ClinVar Miner

Submissions for variant NM_000424.4(KRT5):c.1675C>T (p.Arg559Ter)

gnomAD frequency: 0.00009  dbSNP: rs754242209
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000256176 SCV000321836 likely pathogenic not provided 2023-04-25 criteria provided, single submitter clinical testing Identified in a patient with localized EBS in published literature (Bchetnia et al., 2012); Nonsense variant predicted to result in protein truncation, as the last 32 amino acids are lost; This variant is associated with the following publications: (PMID: 31589614, 21877134)
Labcorp Genetics (formerly Invitae), Labcorp RCV000256176 SCV001025119 likely benign not provided 2017-07-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003401215 SCV004119545 likely pathogenic KRT5-related disorder 2023-03-21 criteria provided, single submitter clinical testing The KRT5 c.1675C>T variant is predicted to result in premature protein termination (p.Arg559*). This variant was reported to occur de novo in a 51 year old individual with moderate localized epidermolysis bullosa simplex (Bchetnia et al 2012. PubMed ID: 21877134). The c.1675C>T variant is located in the last exon of KRT5 and may not result in nonsense-mediated decay. Other frameshift variants reported in this last exon have been reported with autosomal dominant inheritance, but many of them result in amino acid substitutions and extension of the protein (Yalici-Armagan. 2020. PubMed ID: 31965605; Kim. 2017. PubMed ID: 28561874). This variant is reported in 0.011% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-52908824-G-A). We interpret this variant this variant as likely pathogenic.

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