ClinVar

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 126 of the KRT14 protein (p.Leu126Val). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu126 amino acid residue in KRT14. Other variant(s) that disrupt this residue have been observed in individuals with KRT14-related conditions (PMID: 32351751; Invitae), which suggests that this may be a clinically significant amino acid residue. 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 KRT14 protein function. This missense change has been observed in individual(s) with clinical features of autosomal dominant KRT14 related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency).