Total submissions: 7
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, |
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, |
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. |
Gene |
RCV000020296 | SCV000040662 | not provided | Epidermolysis bullosa simplex 1A, generalized severe | no assertion provided | literature only | ||
Epithelial Biology; Institute of Medical Biology, |
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 |