ClinVar Miner

Submissions for variant NM_000094.3(COL7A1):c.7078G>A (p.Gly2360Arg) (rs916512411)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413226 SCV000490506 pathogenic not provided 2017-11-03 criteria provided, single submitter clinical testing The G2360R variant has been published previously in association with dominant dystrophic epidermolysis bullosa (DEB) (Almaani et al., 2011). The G2360R variant is observed in 1/111,666 alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). The G2360R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. This variant occurs at the first Glycine position of the canonical Gly-X-Y repeat in the collagenous domain of the COLVII protein. Glycine substitution variants in this region of the collagen VII protein will destabilize the collagen triple helix resulting in anchoring fibrils that are fragile and result in poor anchoring of the basement membrane to the underlying dermis. A different missense change at this residue (G2360A) has been reported in the published literature in association with recessive DEB (Varki et al., 2007), supporting the functional importance of this region of the protein. We interpret G2360R as a pathogenic variant.
Invitae RCV000413226 SCV001589401 pathogenic not provided 2020-02-14 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 2360 of the COL7A1 protein (p.Gly2360Arg). 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 autosomal dominant and autosomal recessive dystrophic epidermolysis bullosa (PMID: 21448560, 31001817). ClinVar contains an entry for this variant (Variation ID: 372348). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
GenomeConnect, ClinGen RCV001249385 SCV001423380 not provided Dystrophic epidermolysis bullosa no assertion provided phenotyping only Variant interpretted as Pathogenic and reported on 01-21-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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