ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.6187C>T (rs121912849)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413807 SCV000490501 pathogenic not provided 2017-06-15 criteria provided, single submitter clinical testing The R2063W missense variant in the COL7A1 gene has been reported previously in association with autosomal recessive DEB (Hovnanian et al., 1997; Hashimoto et al., 1999; Gardella et al., 2002; Kern et al., 2009; Ben Brick et al., 2014; Kopeckova et al., 2015). The R2063W variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). R2063W is found in the hinge region that interrupts the triple helical domain of the colVII protein and causes destabilization of the triple helix and increased sensitivity to proteolytic degradation. Additionally fibroblasts containing the R2063W variant exhibit decreased motility and adhesion in in vitro assays, which demonstrates that the variant affects the function of the colVII protein and the resulting anchoring fibrils (Woodley et al. 2006). Furthermore, missense variants at the same codon (R2063G) and in nearby residues (G2058A/E, E2059G, G2061V/E, G2064R/V/E, G2067R/A, R2069C) have been reported in the Human Gene Mutation Database in association with DEB (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret R2063W as a pathogenic variant.
Biomedical Innovation Departament, CIEMAT RCV001352769 SCV001547351 pathogenic Dystrophic epidermolysis bullosa 2017-10-31 criteria provided, single submitter research
Invitae RCV000413807 SCV001578934 pathogenic not provided 2020-07-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 2063 of the COL7A1 protein (p.Arg2063Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs121912849, ExAC 0.002%). This variant has been observed in individual(s) with dystrophic epidermolysis bullosa (PMID: 12207583, 9326325, 28830826). 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: 17456). This variant has been reported to affect COL7A1 protein function (PMID: 18450758). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019007 SCV000039294 pathogenic Recessive dystrophic epidermolysis bullosa 2008-02-01 no assertion criteria provided literature only

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