ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.4039G>T (p.Gly1347Trp)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001206925 SCV001378259 likely pathogenic not provided 2020-03-17 criteria provided, single submitter clinical testing This sequence change replaces glycine with tryptophan at codon 1347 of the COL7A1 protein (p.Gly1347Trp). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and tryptophan. This variant is present in population databases (rs121912833, ExAC 0.01%). This variant has been observed in individuals affected with dystrophic epidermolysis bullosa (PMID: 16484981, 18565177). 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.

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