ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.3229G>A (p.Gly1077Ser)

dbSNP: rs886038892
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000252013 SCV000318871 likely pathogenic Cardiovascular phenotype 2013-06-24 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268024 SCV001446607 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute of Human Genetics, University Hospital Muenster RCV002287399 SCV002577894 likely pathogenic See cases 2021-12-21 criteria provided, single submitter clinical testing ACMG categories: PM1,PM2,PM5,PP2,PP3,PP5
Labcorp Genetics (formerly Invitae), Labcorp RCV002518690 SCV003028640 pathogenic Ehlers-Danlos syndrome, type 4 2024-10-05 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1077 of the COL3A1 protein (p.Gly1077Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Ehlers-Danlos syndrome, vascular type (PMID: 31600821). ClinVar contains an entry for this variant (Variation ID: 263685). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt COL3A1 protein function with a positive predictive value of 95%. This variant disrupts the triple helix domain of COL3A1. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL3A1, variants that affect these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic.

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