ClinVar Miner

Submissions for variant NM_000094.3(COL7A1):c.6007G>A (p.Gly2003Arg) (rs121912832)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414493 SCV000490496 pathogenic not provided 2017-04-27 criteria provided, single submitter clinical testing The G2003R pathogenic variant in the COL7A1 gene has been reported previously (Christiano et al 1996). and affects a Glycine residue of the highly conserved Gly-X-Y motif in the collagenous domain which is necessary for stable triple helix winding of the colVII protein. The G2003R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.The G2003R 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R2002C, G2006A,D, R2008G,C) 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. Glycine substitution variants in the COL7A1 can have either autosomal dominant or recessive inheritance patterns and may have either inheritance pattern in different individuals even within the same family (Almaani et al 2011, E Pfendner unpublished), therefore carrier testing of both parents is important in determining recurrence risk. We interpret G2003R as a pathogenic variant.
Ambry Genetics RCV000622440 SCV000740971 pathogenic Inborn genetic diseases 2015-09-01 criteria provided, single submitter clinical testing
OMIM RCV000018976 SCV000039263 pathogenic Dominant dystrophic epidermolysis bullosa with absence of skin 1996-04-01 no assertion criteria provided literature only

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