ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.2915G>C (p.Gly972Ala)

dbSNP: rs587779559
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000087564 SCV001577367 likely pathogenic Ehlers-Danlos syndrome, type 4 2020-06-07 criteria provided, single submitter clinical testing 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly972 amino acid residue in COL3A1. Other variant(s) that disrupt this residue have been observed in individuals with COL3A1-related conditions (PMID: 25758994), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of Ehlers-Danlos syndrome (PMID: 10706896, 24922459, Invitae). This variant is also known as G805A in the literature. ClinVar contains an entry for this variant (Variation ID: 101326). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with alanine at codon 972 of the COL3A1 protein (p.Gly972Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine.
Collagen Diagnostic Laboratory, University of Washington RCV000087564 SCV000120454 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing

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