ClinVar Miner

Submissions for variant NM_000424.4(KRT5):c.1429G>A (p.Glu477Lys)

dbSNP: rs59190510
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000988857 SCV001138749 pathogenic Epidermolysis bullosa simplex 1C, localized 2019-05-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001270733 SCV001451481 pathogenic Epidermolysis bullosa simplex with mottled pigmentation 2019-01-03 criteria provided, single submitter clinical testing Across a selection of literature, the KRT5 c.1429G>A (p.Glu477Lys) missense variant has been reported in a heterozygous state in at least 12 individuals with epidermolysis bullosa simplex (Yasukawa et al. 2006; Jerábková et al. 2010; Sathishkumar et al. 2016; Kim et al. 2017). All patients with this variant were reported to have a severe presentation. The affected parent of one patient was also identified to carry the variant (Sathishkumar et al. 2016). The p.Glu477Lys variant was absent from at least 52 healthy control alleles and is not found in the Genome Aggregation Database. This variant is located in the highly conserved KLLEGE motif. Based on the collective evidence, the p.Glu477Lys variant is classified as pathogenic for epidermolysis bullosa simplex.
Biomedical Innovation Departament, CIEMAT RCV001352787 SCV001547417 pathogenic Epidermolysis bullosa simplex 2019-02-01 criteria provided, single submitter research
Invitae RCV000056565 SCV004294168 pathogenic not provided 2023-06-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 477 of the KRT5 protein (p.Glu477Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant epidermolysis bullosa simplex and/or epidermolysis bullosa simplex (PMID: 9036937, 16098032, 26743602, 31579952). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 21174). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KRT5 protein function. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000020296 SCV000040662 not provided Epidermolysis bullosa simplex 1A, generalized severe no assertion provided literature only
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056565 SCV000087676 not provided not provided no assertion provided not provided
OMIM RCV001811191 SCV002060397 pathogenic Epidermolysis bullosa simplex 2A, generalized severe 2022-02-02 no assertion criteria provided literature only

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