FLNC-related dilated cardiomyopathy is the disease caused by truncating variants in FLNC, the gene encoding filamin C - the large actin cross-linking protein of the striated-muscle Z-disc that is essential for attachment of the sarcomere to the plasma membrane. The entity is named here after the ClinGen gene-disease pair, which the Dilated Cardiomyopathy Gene Curation Expert Panel classifies as Definitive with autosomal dominant inheritance. What defines this entity is an allele-class dichotomy that is unusually clean for a cardiomyopathy gene. Truncating FLNC variants (FLNCtv) act by haploinsufficiency and cause an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathy; non-truncating (predominantly missense) variants instead produce misfolded, aggregate-forming filamin C and cause hypertrophic and restrictive disease with myofibrillar myopathy, curated separately in this knowledge base as Hypertrophic Cardiomyopathy 26 and Myofibrillar Myopathy. The separation is empirical, not theoretical: truncating FLNC variants were absent from 1,078 patients with hypertrophic cardiomyopathy, and myocardial tissue from truncating carriers showed no abnormal filamin C aggregates - the aggregate mechanism of the missense arm is simply not operating. Clinically the disease is high-risk and arrhythmia-led: ventricular arrhythmias and myocardial fibrosis are common, penetrance exceeds 97% after age 40, and malignant ventricular arrhythmia occurs at only mild-to-moderate degrees of left ventricular systolic dysfunction, so ejection-fraction thresholds developed for ordinary dilated cardiomyopathy under-call the need for defibrillator therapy.
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name: FLNC-Related Dilated Cardiomyopathy
creation_date: "2026-08-23T00:00:00Z"
synonyms:
- FLNC-related dilated cardiomyopathy
- truncating FLNC cardiomyopathy
- FLNCtv cardiomyopathy
- filamin C truncating variant cardiomyopathy
- FLNC-related dilated and left-dominant arrhythmogenic cardiomyopathy
description: >-
FLNC-related dilated cardiomyopathy is the disease caused by truncating variants
in FLNC, the gene encoding filamin C - the large actin cross-linking protein of
the striated-muscle Z-disc that is essential for attachment of the sarcomere to
the plasma membrane. The entity is named here after the ClinGen gene-disease
pair, which the Dilated Cardiomyopathy Gene Curation Expert Panel classifies as
Definitive with autosomal dominant inheritance.
What defines this entity is an allele-class dichotomy that is unusually clean for
a cardiomyopathy gene. Truncating FLNC variants (FLNCtv) act by
haploinsufficiency and cause an overlapping phenotype of dilated and
left-dominant arrhythmogenic cardiomyopathy; non-truncating (predominantly
missense) variants instead produce misfolded, aggregate-forming filamin C and
cause hypertrophic and restrictive disease with myofibrillar myopathy, curated
separately in this knowledge base as Hypertrophic Cardiomyopathy 26 and
Myofibrillar Myopathy. The separation is empirical, not theoretical: truncating
FLNC variants were absent from 1,078 patients with hypertrophic cardiomyopathy,
and myocardial tissue from truncating carriers showed no abnormal filamin C
aggregates - the aggregate mechanism of the missense arm is simply not operating.
Clinically the disease is high-risk and arrhythmia-led: ventricular arrhythmias
and myocardial fibrosis are common, penetrance exceeds 97% after age 40, and
malignant ventricular arrhythmia occurs at only mild-to-moderate degrees of left
ventricular systolic dysfunction, so ejection-fraction thresholds developed for
ordinary dilated cardiomyopathy under-call the need for defibrillator therapy.
category: Genetic
classifications:
harrisons_chapter:
- classification_value: CARDIOVASCULAR
- classification_value: GENETICS_ENVIRONMENT_DISEASE
disease_term:
preferred_term: FLNC-related dilated cardiomyopathy
parents:
- Dilated Cardiomyopathy
- Genetic Disorder
inheritance:
- name: Autosomal dominant
description: >-
Truncating FLNC variants cosegregate with the dilated and left-dominant
arrhythmogenic phenotype in a dominant pattern, with a combined LOD score of
9.5 across the founding families. Penetrance is high and age-dependent,
exceeding 97% in carriers older than 40 years - substantially higher than in
most other genetic dilated cardiomyopathies, which is why cascade screening
with longitudinal follow-up matters in these families.
inheritance_term:
preferred_term: Autosomal dominant inheritance
term:
id: HP:0000006
label: Autosomal dominant inheritance
penetrance: INCOMPLETE
penetrance_percentage: ">97% after age 40"
evidence:
- reference: CGGV:assertion_edb5197f-05dc-42a4-a497-fff472985c6b-2025-05-30T160000.000Z
reference_title: "FLNC / dilated cardiomyopathy (Definitive)"
supports: SUPPORT
evidence_source: OTHER
snippet: "FLNC | HGNC:3756 | dilated cardiomyopathy | MONDO:0005021 | AD | Definitive"
explanation: >-
ClinGen's Dilated Cardiomyopathy Gene Curation Expert Panel classifies the
FLNC-dilated cardiomyopathy relationship as Definitive with autosomal
dominant inheritance. This assertion is the basis for the entity's name and
scope.
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Truncating mutations in FLNC cosegregated with this phenotype with a dominant
inheritance pattern (combined logarithm of the odds score: 9.5).
explanation: >-
Documents dominant cosegregation with a strong combined LOD score across the
founding families.
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Penetrance was >97% in carriers older than 40 years."
explanation: >-
Quantifies the high age-dependent penetrance that distinguishes this entity
from most other genetic dilated cardiomyopathies.
prevalence:
- population: Genetic dilated cardiomyopathy
measure_type: UNKNOWN
prevalence_class: UNKNOWN
notes: >-
FLNC is now regarded as one of the more prevalent genetic causes of dilated
cardiomyopathy, but no population-based rate is established for the
truncating-FLNC entity specifically.
evidence:
- reference: PMID:32112656
reference_title: "A mutation update for the FLNC gene in myopathies and cardiomyopathies."
supports: SUPPORT
evidence_source: OTHER
snippet: "FLNC variants are now among the more prevalent causes of genetic DCM."
explanation: >-
States FLNC's standing among genetic causes of dilated cardiomyopathy.
Evidence source is OTHER because this is a mutation-update review.
pathophysiology:
- name: FLNC Truncating Variant Causing Filamin C Haploinsufficiency
biological_scale: MOLECULAR
role: trigger
conforms_to: "cardiomyopathy_maladaptive_remodeling#Primary Cardiomyocyte Insult"
description: >-
The initiating lesion is a truncating variant in FLNC - nonsense, frameshift or
splice-disrupting - which acts by haploinsufficiency, reducing the amount of
functional filamin C rather than introducing a misfolding protein into the
Z-disc. This is the mechanistic fork that separates the entity from the
non-truncating FLNC diseases: myocardial tissue from truncating carriers shows
no abnormal filamin C aggregates, so the aggregation mechanism that drives the
missense hypertrophic and myofibrillar phenotypes is not operating here.
genes:
- preferred_term: FLNC
term:
id: hgnc:3756
label: FLNC
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
molecular_functions:
- preferred_term: Actin filament binding
term:
id: GO:0051015
label: actin filament binding
modifier: DECREASED
cellular_components:
- preferred_term: Z disc
term:
id: GO:0030018
label: Z disc
evidence:
- reference: PMID:32112656
reference_title: "A mutation update for the FLNC gene in myopathies and cardiomyopathies."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Truncating variants with subsequent haploinsufficiency are associated with DCM
and cardiac arrhythmias.
explanation: >-
States the operative mechanism of the truncating allele class -
haploinsufficiency - and its association with the dilated and arrhythmic
phenotype. Evidence source is OTHER because this is a mutation-update review.
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Immunohistochemical staining of myocardial tissue showed no abnormal filamin C
aggregates in patients with truncating FLNC mutations.
explanation: >-
Direct human myocardial evidence that the aggregate mechanism of the
non-truncating FLNC diseases is absent in truncating carriers - the
observation that separates this entity from Hypertrophic Cardiomyopathy 26 at
the level of mechanism rather than phenotype alone.
downstream:
- target: Failure of Sarcomere Attachment to the Sarcolemma
causal_link_type: DIRECT
description: >-
Reduced filamin C degrades the Z-disc linkage that anchors the sarcomere to
the plasma membrane.
- name: Failure of Sarcomere Attachment to the Sarcolemma
biological_scale: CELLULAR
role: effector
description: >-
Filamin C cross-links actin at the Z-disc and is essential for attachment of
the sarcomere to the plasma membrane, coupling contractile force to the cell
surface and the surrounding matrix. Halving the available protein degrades that
linkage, so force generated by an intact contractile apparatus is transmitted
poorly to and between cells. The lesion is one of mechanical coupling rather
than of force generation, calcium regulation or protein quality control.
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
biological_processes:
- preferred_term: Actin Filament Bundle Assembly
term:
id: GO:0051017
label: actin filament bundle assembly
modifier: ABNORMAL
- preferred_term: Sarcomere Organization
term:
id: GO:0045214
label: sarcomere organization
modifier: ABNORMAL
cellular_components:
- preferred_term: Z disc
term:
id: GO:0030018
label: Z disc
evidence:
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to
the plasmatic membrane.
explanation: >-
Establishes the specific cellular function - sarcomere-to-sarcolemma
attachment - whose loss constitutes this node.
downstream:
- target: Myocardial Fibrosis and Ventricular Dilation
causal_link_type: DIRECT
description: >-
Defective mechanical coupling drives fibrotic replacement and chamber
dilation with systolic impairment.
- name: Myocardial Fibrosis and Ventricular Dilation
biological_scale: TISSUE
role: central_effector
conforms_to: "cardiomyopathy_maladaptive_remodeling#Ventricular Remodeling"
description: >-
The tissue phenotype is a left-dominant, fibrosis-heavy remodelling: in the
founding cohort left ventricular dilation was present in 68% of carriers,
systolic dysfunction in 46%, and myocardial fibrosis in 67%. The prominence of
fibrosis relative to the degree of systolic impairment is characteristic and is
what gives the disease its overlap with arrhythmogenic cardiomyopathy: the
electrocardiographic signature of that overlap - inferolateral negative T waves
and low QRS voltages - was present in a third of carriers.
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
- preferred_term: Cardiac Fibroblast
term:
id: CL:0002548
label: fibroblast of cardiac tissue
biological_processes:
- preferred_term: Extracellular Matrix Organization
term:
id: GO:0030198
label: extracellular matrix organization
modifier: INCREASED
- preferred_term: Heart Contraction
term:
id: GO:0060047
label: heart contraction
modifier: DECREASED
locations:
- preferred_term: Left ventricle
term:
id: UBERON:0002084
label: heart left ventricle
evidence:
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The phenotype consisted of left ventricular dilation (68%), systolic
dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T
waves and low QRS voltages on electrocardiography (33%)
explanation: >-
Quantifies the tissue-level phenotype - dilation, systolic dysfunction and the
prominent myocardial fibrosis - together with the arrhythmogenic-cardiomyopathy
ECG signature.
downstream:
- target: Arrhythmogenic Substrate and Malignant Ventricular Arrhythmia
causal_link_type: DIRECT
description: >-
Fibrotic, electrically heterogeneous myocardium supports malignant ventricular
arrhythmia.
- name: Arrhythmogenic Substrate and Malignant Ventricular Arrhythmia
biological_scale: ORGANISM
role: amplifier
description: >-
The defining clinical feature of the entity. Ventricular arrhythmias occurred in
82% of carriers in the founding cohort, and malignant ventricular arrhythmia
occurs at only mild-to-moderate degrees of left ventricular systolic
dysfunction - so arrhythmic risk is not tracked by ejection fraction, as it is
in ordinary dilated cardiomyopathy. FLNC sits with desmoplakin, lamin A/C,
phospholamban, RBM20 and TMEM43 among the arrhythmogenic left ventricular
cardiomyopathy genes for which left ventricular systolic function is an
insensitive predictor of risk.
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
biological_processes:
- preferred_term: Cardiac Conduction
term:
id: GO:0061337
label: cardiac conduction
modifier: ABNORMAL
evidence:
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in
21 of 28 families)
explanation: >-
Quantifies the arrhythmic burden and the sudden-death toll across the founding
families.
- reference: PMID:33978673
reference_title: "Association of Left Ventricular Systolic Dysfunction Among Carriers of Truncating Variants in Filamin C With Frequent Ventricular Arrhythmia and End-stage Heart Failure."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Truncating variants in the gene encoding filamin C (FLNCtv) are associated
with arrhythmogenic and dilated cardiomyopathies with a reportedly high risk
of ventricular arrhythmia.
explanation: >-
Independent cohort confirmation of the high ventricular-arrhythmia risk of the
truncating-FLNC phenotype.
- reference: PMID:37558308
reference_title: "Genetic Risk Stratification in Arrhythmogenic Left Ventricular Cardiomyopathy."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
left ventricular systolic function is an insensitive predictor of risk in
patients with these genetic diagnoses
explanation: >-
Places FLNC among the arrhythmogenic left ventricular cardiomyopathy genes for
which ejection fraction does not capture arrhythmic risk - the clinically
decisive point for this entity.
downstream:
- target: Sudden Cardiac Death and End-Stage Heart Failure
causal_link_type: DIRECT
- name: Sudden Cardiac Death and End-Stage Heart Failure
biological_scale: ORGANISM
role: consequence
conforms_to: "cardiomyopathy_maladaptive_remodeling#Structural Cardiac Impairment and Heart Failure"
description: >-
The endpoint has two arms, and the arrhythmic one frequently arrives first:
sudden cardiac death was frequent across the founding families, and in a later
cohort adverse events comprised both malignant ventricular arrhythmia and
end-stage heart failure. Because arrhythmic death can precede severe systolic
impairment, prompt defibrillator implantation is recommended for affected
truncating-variant carriers, and higher ejection-fraction thresholds than those
currently recommended should be considered for prophylactic implantation.
cell_types:
- preferred_term: Cardiomyocyte
term:
id: CL:0000746
label: cardiac muscle cell
biological_processes:
- preferred_term: Heart Contraction
term:
id: GO:0060047
label: heart contraction
modifier: ABNORMAL
evidence:
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Truncating mutations in FLNC caused an overlapping phenotype of dilated and
left-dominant arrhythmogenic cardiomyopathies complicated by frequent
premature sudden death.
explanation: >-
States the composite endpoint - dilated plus left-dominant arrhythmogenic
disease complicated by frequent premature sudden death.
- reference: PMID:33978673
reference_title: "Association of Left Ventricular Systolic Dysfunction Among Carriers of Truncating Variants in Filamin C With Frequent Ventricular Arrhythmia and End-stage Heart Failure."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The high frequency of MVA among patients with FLNCtv with mild to moderate
LVSD suggests that higher LVEF values than those currently recommended should
be considered for prophylactic implantable cardioverter-defibrillator therapy
in FLNCtv carriers.
explanation: >-
The management-changing finding: malignant ventricular arrhythmia occurs at
mild-to-moderate systolic dysfunction, so conventional ejection-fraction
thresholds under-call the need for prophylactic defibrillator therapy.
phenotypes:
- name: Dilated Cardiomyopathy
category: Cardiovascular
description: >-
Left ventricular dilation with systolic dysfunction, present in roughly
two-thirds and half of carriers respectively in the founding cohort.
phenotype_term:
preferred_term: Dilated cardiomyopathy
term:
id: HP:0001644
label: Dilated cardiomyopathy
evidence:
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The phenotype consisted of left ventricular dilation (68%), systolic
dysfunction (46%), and myocardial fibrosis (67%)
explanation: >-
Quantifies left ventricular dilation in truncating-FLNC carriers.
- name: Myocardial Fibrosis
category: Cardiovascular
description: >-
Myocardial fibrosis is prominent and disproportionate to the degree of systolic
impairment, and is the substrate linking this entity to arrhythmogenic
cardiomyopathy.
phenotype_term:
preferred_term: Myocardial fibrosis
term:
id: HP:0001685
label: Myocardial fibrosis
frequency: FREQUENT
evidence:
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The phenotype consisted of left ventricular dilation (68%), systolic
dysfunction (46%), and myocardial fibrosis (67%)
explanation: >-
The reported 67% frequency of myocardial fibrosis maps to the FREQUENT band.
- name: Ventricular Arrhythmia
category: Cardiovascular
description: >-
Ventricular arrhythmias are the dominant clinical feature, occurring in the
large majority of carriers and at only mild-to-moderate systolic dysfunction.
phenotype_term:
preferred_term: Ventricular arrhythmia
term:
id: HP:0004308
label: Ventricular arrhythmia
frequency: VERY_FREQUENT
evidence:
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in
21 of 28 families)
explanation: >-
The reported 82% frequency of ventricular arrhythmias maps to the
VERY_FREQUENT band.
- name: Left Ventricular Systolic Dysfunction
category: Cardiovascular
description: >-
Systolic impairment occurs in about half of carriers, and malignant arrhythmia
can occur while it is still only mild to moderate.
phenotype_term:
preferred_term: Left ventricular systolic dysfunction
term:
id: HP:0025169
label: Left ventricular systolic dysfunction
evidence:
- reference: PMID:33978673
reference_title: "Association of Left Ventricular Systolic Dysfunction Among Carriers of Truncating Variants in Filamin C With Frequent Ventricular Arrhythmia and End-stage Heart Failure."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The high frequency of MVA among patients with FLNCtv with mild to moderate
LVSD suggests that higher LVEF values than those currently recommended should
be considered for prophylactic implantable cardioverter-defibrillator therapy
in FLNCtv carriers.
explanation: >-
Documents that malignant ventricular arrhythmia occurs at mild-to-moderate
left ventricular systolic dysfunction in these carriers.
- name: Sudden Cardiac Death
category: Cardiovascular
description: >-
Premature sudden cardiac death is frequent and may be the presenting event.
phenotype_term:
preferred_term: Sudden cardiac death
term:
id: HP:0001645
label: Sudden cardiac death
evidence:
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Truncating mutations in FLNC caused an overlapping phenotype of dilated and
left-dominant arrhythmogenic cardiomyopathies complicated by frequent
premature sudden death.
explanation: >-
Documents frequent premature sudden death as a defining feature of the entity.
- name: Congestive Heart Failure
category: Cardiovascular
description: >-
End-stage heart failure is the second arm of the endpoint, alongside malignant
arrhythmia.
phenotype_term:
preferred_term: Congestive heart failure
term:
id: HP:0001635
label: Congestive heart failure
evidence:
- reference: PMID:33978673
reference_title: "Association of Left Ventricular Systolic Dysfunction Among Carriers of Truncating Variants in Filamin C With Frequent Ventricular Arrhythmia and End-stage Heart Failure."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
29 patients (17.4%) reached the primary end point (19 patients with MVA and 10
patients with end-stage heart failure)
explanation: >-
Quantifies end-stage heart failure alongside malignant ventricular arrhythmia
as the composite adverse endpoint in a follow-up cohort.
genetic:
- name: FLNC
gene_term:
preferred_term: FLNC
term:
id: hgnc:3756
label: FLNC
relationship_type: CAUSATIVE
frequency: >-
One of the more prevalent genetic causes of dilated cardiomyopathy, though
no case fraction for the truncating-FLNC entity specifically has been
reported in a screened cohort.
evidence:
- reference: CGGV:assertion_edb5197f-05dc-42a4-a497-fff472985c6b-2025-05-30T160000.000Z
reference_title: "FLNC / dilated cardiomyopathy (Definitive)"
supports: SUPPORT
evidence_source: OTHER
snippet: >-
FLNC | HGNC:3756 | dilated cardiomyopathy | MONDO:0005021 | AD |
Definitive
explanation: >-
ClinGen's Gene Curation Expert Panel classifies this gene-disease
relationship as Definitive, which is the authority for curating the gene
as CAUSATIVE rather than a candidate.
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Truncating mutations in FLNC cosegregated with this phenotype with a
dominant inheritance pattern (combined logarithm of the odds score:
9.5).
explanation: >-
Cosegregation at a combined LOD of 9.5 is the statistical basis for the
gene-disease relationship and for restricting it to the truncating
allele class.
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Penetrance was >97% in carriers older than 40 years.
explanation: >-
Gene-level penetrance in carriers over 40, which with the age dependence
is what makes cascade screening of adult relatives worthwhile.
- reference: PMID:32112656
reference_title: "A mutation update for the FLNC gene in myopathies and cardiomyopathies."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
FLNC variants are now among the more prevalent causes of genetic DCM.
explanation: >-
Supports the qualitative frequency band only. Curated PARTIAL because it
is a comparative statement about prevalence among genetic dilated
cardiomyopathy causes and carries no denominator, which is why no
case_fractions record is recorded.
treatments:
- name: Implantable Cardioverter-Defibrillator
description: >-
Prompt defibrillator implantation should be considered in affected carriers of
truncating FLNC variants, and prophylactic implantation should be considered at
higher ejection-fraction values than conventional thresholds, because malignant
ventricular arrhythmia occurs at mild-to-moderate systolic dysfunction.
therapeutic_modality: DEVICE
treatment_term:
preferred_term: implantable cardioverter-defibrillator placement
term:
id: NCIT:C80435
label: Implantable Cardioverter-Defibrillator Placement
evidence:
- reference: PMID:27908349
reference_title: "Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Prompt implantation of a cardiac defibrillator should be considered in
affected patients harboring truncating mutations in FLNC.
explanation: >-
The founding study's explicit management recommendation for this entity.
- reference: PMID:33978673
reference_title: "Association of Left Ventricular Systolic Dysfunction Among Carriers of Truncating Variants in Filamin C With Frequent Ventricular Arrhythmia and End-stage Heart Failure."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The high frequency of MVA among patients with FLNCtv with mild to moderate
LVSD suggests that higher LVEF values than those currently recommended should
be considered for prophylactic implantable cardioverter-defibrillator therapy
in FLNCtv carriers.
explanation: >-
Supports raising the ejection-fraction threshold for prophylactic
defibrillator therapy in this genotype.
- name: Heart Failure Pharmacotherapy
description: >-
Standard guideline-directed heart-failure therapy addresses the systolic arm of
the phenotype.
therapeutic_modality: SMALL_MOLECULE
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
- name: Heart Transplantation
description: >-
Transplantation is the option for end-stage heart failure, which was a component
of the adverse endpoint in follow-up cohorts.
therapeutic_modality: SURGERY
treatment_term:
preferred_term: organ transplantation
term:
id: NCIT:C15289
label: Organ Transplantation
references:
- reference: PMID:20301486
title: Dilated Cardiomyopathy Overview.
tags:
- GeneReviews
notes: >-
Naming and mapping. The entity is named after the ClinGen gene-disease pair
("FLNC / dilated cardiomyopathy", Definitive, autosomal dominant, Dilated
Cardiomyopathy Gene Curation Expert Panel), following the ClinGen convention of
curating a gene against a disease entity rather than against a numbered
phenotypic-series locus. The `disease_term` is deliberately left unmapped: there
is no numbered CMD class in MONDO for FLNC-related dilated cardiomyopathy, and
the available alternatives are each wrong in a different way - MONDO:0016189
(qualitative or quantitative defects of filamin C) is a filaminopathy class
spanning the myopathies rather than a cardiomyopathy entity, while MONDO:0005021
(dilated cardiomyopathy) is the general umbrella already carried by the DisMech
umbrella entry. Recording no term is more honest than asserting a mapping the
concept does not have.
Scope, and its relation to the other FLNC entries. This entry covers the
TRUNCATING allele class only. The dichotomy is the entity's defining feature and
is evidenced rather than assumed: truncating variants act by haploinsufficiency
and were absent from 1,078 hypertrophic cardiomyopathy patients, and truncating
carriers' myocardium shows no abnormal filamin C aggregates. The non-truncating
(predominantly missense) allele class, which produces misfolded aggregate-forming
filamin C, is curated separately as `Hypertrophic Cardiomyopathy 26` and, for the
skeletal-muscle-predominant presentation, `Myofibrillar Myopathy`. The three
entries partition the FLNC allele spectrum rather than overlapping.
Grouping membership deliberately withheld. This entry is NOT a member of the
`Familial Dilated Cardiomyopathy` grouping, for two reasons. Its phenotype is an
overlapping dilated and left-dominant *arrhythmogenic* cardiomyopathy rather than
an isolated dilated one, so it sits outside that grouping's "isolated" clause;
and the grouping's mapping records a verified CONSISTENT relationship in which
every member is a direct MONDO child of MONDO:0700335, which an unmapped entry
cannot satisfy. Admitting it would weaken a claim the grouping currently makes
honestly.
Clinical caveat worth preserving: arrhythmic risk in this entity is not tracked
by ejection fraction. Malignant ventricular arrhythmia occurs at mild-to-moderate
systolic dysfunction, so conventional EF-based thresholds for prophylactic
defibrillator therapy under-call it - the same property recorded for RBM20
(CMD1DD) and the other arrhythmogenic left ventricular cardiomyopathy genes.
GeneReviews scope. The GeneReviews resource applicable to this entry is the
disease-level "Dilated Cardiomyopathy Overview" (PMID:20301486), tagged
accordingly in `references`. Its indexed PubMed record is content_type
abstract_only and carries only the chapter's purpose statement, not the
Clinical Characteristics, Management, or Genetic Counseling sections, so
section-by-section GeneReviews mining is not possible from the cache and no
snippet is quoted from it. The clinical-characteristics baseline for this
entry is therefore built from the primary FLNC cohort and pedigree literature
cited throughout, principally PMID:27908349, PMID:33978673.