| Variant (HGVS; transcript if given) | Zygosity | Variant class | Main reported clinical features | Key biochemical diagnostic findings | Source (paper, year) | URL / DOI | Notes |
|---|---|---|---|---|---|---|---|
| c.2659_2660insC in **COG1** (older nomenclature in discovery paper); predicted frameshift from aa 888 with premature stop/truncated C-terminus | Homozygous | Frameshift, truncating, presumed loss-of-function | First reported patient: feeding problems, failure to thrive, generalized hypotonia, small hands/feet, facial dysmorphism, rhizomelic short stature, progressive microcephaly, mild psychomotor retardation, mild hepatosplenomegaly (pqac-00000001, pqac-00000003, pqac-00000004) | Type II serum transferrin IEF with reduction of penta-/hexasialotransferrin and increase of asialo-/mono-/di-/trisialotransferrin; abnormal ApoC-III with ApoC-III0 band; reduced incorporation of [3H]UDP-galactose and [3H]CMP-neuraminic acid; undersialylation/undergalactosylation of serum N-glycans (pqac-00000001, pqac-00000011) | Foulquier et al., 2006 | https://doi.org/10.1073/pnas.0507685103 | Original discovery report; wild-type COG1 restored β1,4-galactosyltransferase localization; quantified Golgi enzyme decreases included 55% for mannosidase II and 67% for β1,4-galactosyltransferase I (pqac-00000003, pqac-00000013) |
| NM_018714.3: c.2665dup; p.(Arg889Profs*12) | Homozygous | Frameshift, truncating | Neonatal multifocal clonic seizures, hypotonia, weakness, absent reflexes, feeding/swallowing disorder, developmental delay, progressive microcephaly, dysmorphic facial features, adducted thumbs, widely spaced nipples, tibial bowing/curvature, dysmorphic corpus callosum and frontal atrophy/thin corpus callosum on MRI, hepatitis/liver involvement; later milder course with independent gait at 1 year 10 months in one proband (pqac-00000002, pqac-00000018, pqac-00000020) | Type II serum transferrin isoelectrofocusing pattern with increased trisialo-, disialo-, monosialo-, and asialo-transferrin and decreased tetrasialotransferrin; marked transaminase elevations reported (AST up to 1108 U/L, ALT 169 U/L) (pqac-00000000, pqac-00000002, pqac-00000018) | Salazar et al., 2021 | https://doi.org/10.1111/cge.13980 | Review states COG1-CDG reported in 5 patients; same variant reported in at least 2 homozygous patients. gnomAD frequency reported as 6/251,390 alleles overall (heterozygous) and 5/34,590 alleles in Latino/Admixed American population in one summary (pqac-00000000, pqac-00000002, pqac-00000018) |
| c.1070+5G>A | Homozygous | Canonical/near-canonical splice donor variant causing exon 6 skipping, frameshift, premature stop in exon 7 | Two patients with cerebrocostomandibular-like syndrome / severe multisystem COG1-CDG: prenatal growth impairment, hearing impairment, cryptorchidism, renal involvement, skeletal abnormalities including costovertebral dysplasia, delayed walking and speech; associated with more severe phenotype than c.2665dup cases (pqac-00000018, pqac-00000020) | Not specifically detailed in the extracted Zeevaert evidence here; COG1-CDG in general shows type II glycosylation abnormalities and delayed retrograde trafficking in patient fibroblasts (pqac-00000007, pqac-00000010) | Zeevaert et al., 2009; summarized in Salazar et al., 2021 | https://doi.org/10.1093/hmg/ddn379 ; https://doi.org/10.1111/cge.13980 | Zeevaert abstract: intronic mutation disrupted splice donor, leaving only ~3% normal transcript in one patient and showing delay in retrograde trafficking by Brefeldin A assay (pqac-00000007); older patients in review were aged 12.5 and 14 years (pqac-00000018) |
| c.1070+3A>G | Heterozygous in compound heterozygous state | Splice-region variant | In Huang case: recurrent cyanosis, poor responsiveness, neonatal hypoglycemia from day 2 of life, recurrent hypoglycemic episodes after discharge, developmental/motor retardation, epilepsy/convulsions, strabismus; literature review also notes dysmorphic and neurologic findings in COG1-CDG such as microcephaly and macular lesions (pqac-00000019) | Paper states patient was diagnosed as CDG-IIg; specific transferrin profile not extracted in gathered evidence for this row (pqac-00000019) | Huang et al., 2021 | https://doi.org/10.1186/s12887-021-02922-7 | Maternal allele in reported compound heterozygous proband; authors proposed hypoglycemia may relate to altered insulin secretion, but this remains speculative (pqac-00000019) |
| c.2492G>A; p.(Arg831Gln) | Heterozygous in compound heterozygous state | Missense; proposed pathogenic / potential pathogenetic variant | Same Huang proband as above: developmental retardation, convulsion/epilepsy, strabismus, neonatal and recurrent hypoglycemia (pqac-00000008, pqac-00000019) | Paper states CDG-IIg diagnosis after genetic and clinical evaluation; specific glycosylation assay details were not extracted in gathered evidence (pqac-00000008, pqac-00000019) | Huang et al., 2021 | https://doi.org/10.1186/s12887-021-02922-7 | Paternally inherited allele; authors state p.Arg831Gln “may be a potential pathogenetic variant” and that only a very small number of CDG-IIg cases had been reported previously (pqac-00000008, pqac-00000019) |
| NM_018714.3: c.1049C>T; p.(Thr350Met) | Reported as homozygous in prior literature/database discussion | Missense | Evidence for pathogenicity is weak in gathered evidence; no specific clinical phenotype extracted for a confirmed affected case in the current evidence set (pqac-00000002) | Not established from gathered evidence | Salazar et al., 2021 | https://doi.org/10.1111/cge.13980 | Mentioned as the only reported missense in COG1, but also noted to be homozygous in gnomAD and therefore likely benign / uncertain rather than clearly pathogenic; included here for completeness and caution, not as a firmly established disease-causing allele (pqac-00000000, pqac-00000002) |


*Table: This table compiles the COG1-CDG/CDG-IIg variants supported by the gathered evidence, together with zygosity, variant class, phenotype, and diagnostic findings. It highlights the small number of reported pathogenic truncating/splice variants, the Huang compound-heterozygous case, and key biochemical hallmarks such as the type II transferrin profile.*