Submissions for variant NM_000526.5(KRT14):c.1186C>T (p.Gln396Ter)

dbSNP: rs58393329

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV001823105	SCV002072851	likely pathogenic	Epidermolysis bullosa simplex 1C, localized		criteria provided, single submitter	clinical testing	The stop gained p.Q396* in KRT14 (NM_000526.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through protein truncation.The variant has been submitted to ClinVar but has not been classified. The CADD score is deleterious and the residue is conserved across species. For these reasons, this variant has been classified as Likely Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV003338401	SCV004048116	likely pathogenic	Epidermolysis bullosa simplex 1A, generalized severe		criteria provided, single submitter	clinical testing	The stop gained p.Q396* in KRT14 (NM_000526.5) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. The p.Q396* variant is a loss of function variant in the gene KRT14, which is intolerant of Loss of Function variants. The nucleotide change in KRT14 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV003338402	SCV004048423	uncertain significance	Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive	2023-06-02	criteria provided, single submitter	clinical testing	The observed stop gained variant c.1186C>T(p.Gln396Ter) in the KRT14 gene has been reported previously in homozygous and heterozygous state in multiple Israeli individuals affected with Epidermolysis bullosa simplex and is suggestive of a founder effect in this population (Ciubotaru D, et al., 2003). This variant is reported with the allele frequency 0.0004% in the gnomAD Exomes. It is submitted to ClinVar as Likely Pathogenic. Computational evidence (MutationTaster - Disease causing) predicts damaging effect on protein structure and function for this variant. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Epithelial Biology; Institute of Medical Biology, Singapore	RCV000056672	SCV000087785	not provided	not provided		no assertion provided	not provided