ClinVar

Description

Variant summary: SLC26A4 c.1146C>G (p.Asn382Lys) results in a non-conservative amino acid change located in the SLC26A/SulP transporter domain (IPR011547) of 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 8e-06 in 251150 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1146C>G has been reported in the literature as a non-informative genotype (second allele not specified) in at-least one individual affected with prelingual sensorineural hearing loss (SNHL) who was previously screened negative for GJB2, GJB6 and MT-RNR1 genes (example, Carvalho_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Pendred Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.