ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.6044G>T (p.Gly2015Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biomedical Innovation Departament, CIEMAT RCV001352758 SCV001547340 pathogenic Dystrophic epidermolysis bullosa 2018-12-01 criteria provided, single submitter research
Invitae RCV001378163 SCV001575673 likely pathogenic not provided 2020-08-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 2015 of the COL7A1 protein (p.Gly2015Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of autosomal dominant epidermolysis bullosa dystrophica (PMID: 16971478). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL7A1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Gly2015 amino acid residue in COL7A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID:21448560, 9668111,19726672). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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