ClinVar Miner

Submissions for variant NM_000094.3(COL7A1):c.7957G>A (p.Gly2653Arg) (rs121912851)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001203194 SCV001374346 likely pathogenic not provided 2020-08-26 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 2653 of the COL7A1 protein (p.Gly2653Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with recessive dystrophic epidermolysis bullosa (PMID: 8644729, 31001817). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 17458). 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). 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 missense variants at these glycine residues in COL7A1 are more frequently observed in individuals with disease than in the general population (PMID: 22058051). 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 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.
OMIM RCV000019009 SCV000039296 pathogenic Recessive dystrophic epidermolysis bullosa 1996-04-01 no assertion criteria provided literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001203194 SCV001739812 pathogenic not provided no assertion criteria provided clinical testing

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