ClinVar Miner

Submissions for variant NM_000424.4(KRT5):c.1427G>A (p.Gly476Asp)

dbSNP: rs56922686
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, Singapore RCV000056563 SCV000087674 not provided not provided no assertion provided not provided

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