Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000056563 | SCV001774104 | pathogenic | not provided | 2023-02-06 | criteria provided, single submitter | clinical testing | Located within the 2B helix-termination motif, a critical functional domain that is intolerant of change and conserved across species (Chamcheu et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21176769, 25017986, 16439963, 17549391, 21375516, 26432462, 31312705, 26167768) |
Mendelics | RCV002247452 | SCV002516640 | pathogenic | Epidermolysis bullosa simplex 1A, generalized severe | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000056563 | SCV004294169 | pathogenic | not provided | 2022-11-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 KRT5 protein function. ClinVar contains an entry for this variant (Variation ID: 66215). This missense change has been observed in individual(s) with autosomal dominant epidermolysis bullosa simplex (PMID: 16439963, 17549391, 21375516). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 476 of the KRT5 protein (p.Gly476Asp). |
Epithelial Biology; Institute of Medical Biology, |
RCV000056563 | SCV000087674 | not provided | not provided | no assertion provided | not provided |