ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.497dupA (rs766902987)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000268681 SCV000329312 pathogenic not provided 2019-01-09 criteria provided, single submitter clinical testing The c.497dupA pathogenic variant in the COL7A1 gene has been reported previously either in the homozygous state or with another COL7A1 variant in multiple individuals with dystrophic epidermolysis bullosa (DEB), and is a founder variant in the Italian population (Christiano et al., 1996, Gardella et al 2002; Kern et al., 2006; Varki et al 2007; van den Akker et al., 2009; Tenedini et al., 2015; Diociaiuti et al., 2016; Kopeckova et al., 2016). The c.497dupA variant causes a frameshift starting with codon Valine 168, changes this amino acid to a Glycine residue and creates a premature Stop codon at position 12 of the new reading frame, denoted p.Val168GlyfsX12. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.497dupA variant is observed in 8/111,514 (0.007%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016), consistent with its prevalence in the Italian and American populations. We interpret c.497dupA as a pathogenic variant.
Invitae RCV000268681 SCV001230096 pathogenic not provided 2020-03-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val168Glyfs*12) in the COL7A1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs766902987, ExAC 0.009%). This variant has been observed in individual(s) with dystrophic epidermolysis bullosa (PMID: 26864810, 21448560, 8618004). ClinVar contains an entry for this variant (Variation ID: 279784). Loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478). For these reasons, this variant has been classified as Pathogenic.
Biomedical Innovation Departament, CIEMAT RCV001352748 SCV001547281 pathogenic Dystrophic epidermolysis bullosa 2019-01-31 criteria provided, single submitter research

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