ClinVar

Description

The c.6527dupC (p.Gly2177Trpfs*113) frameshift variant in the COL7A1 gene has been previously reported in at least 27 affected individuals with autosomal recessive Dystrophic Epidermolysis Bullosa and is predicted to prematurely truncate the protein. Affected individuals have harbored this frameshift variant in trans with a splice-site variant (7930-1G>C) and several missense variants (G2587D, G2434R, G2366D, G1383R) (Hovnanian et al., 1997; Cuadrado-Corrales et al., 2010; Kern et al. 2006). Loss of functions variants have been described in the COL7A1 gene in several affected individuals (OMIM#: 120120) and are, therefore, a common mechanism of disease. Functional studies have shown gene and protein expression are not detectable when this variant is present (Hovnanian et al., 1997; Cuadrado-Corrales et al., 2010).This c.6527dupC variant is absent from two control population databases (Exome Sequencing Project [ESP] and 1000 Genomes) and present at a low frequency in a third control population database (ExAC = 0.044%). In silico algorithms predict the nucleotide position where this variant occurs is conserved (GERP = 4.53). Therefore, this collective evidence supports the classification of the c.6527dupC (p.Gly2177Trpfs*113) as a recessive Pathogenic variant for Dystrophic Epidermolysis Bullosa.