ClinVar Miner

Submissions for variant NM_000093.5(COL5A1):c.2332G>T (p.Gly778Cys)

dbSNP: rs2132747882
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centogene AG - the Rare Disease Company RCV001808975 SCV002059283 likely pathogenic Ehlers-Danlos syndrome, classic type, 1 2020-04-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001808975 SCV004309185 uncertain significance Ehlers-Danlos syndrome, classic type, 1 2023-07-19 criteria provided, single submitter clinical testing Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1333760). This variant has not been reported in the literature in individuals affected with COL5A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 778 of the COL5A1 protein (p.Gly778Cys). This variant disrupts the triple helix domain of COL5A1. 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), and variants at these glycine residues in COL5A1 are more frequently observed in individuals with disease than in the general population (PMID: 22696272, 23587214). However, the clinical significance of this observation remains uncertain since only a limited number of affected individuals have been described to date. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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