ClinVar

Description

Variant summary: BSND c.35T>C (p.Ile12Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251442 control chromosomes. c.35T>C has been reported in the literature as homozygous genotypes in individuals affected with non-syndromic deafness and as a compound heterozygous genotype with another loss of function variant, c.10G>T (p.E4*), in individuals with features of Bartter Syndrome, Type 4a (example, Riazuddin_2009). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function demonstrating intact chloride channel function and impaired chaperone function of the protein in intracellular trafficking (Riazuddin_2009). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.