ClinVar

Description

Variant summary: SLC26A4 c.2090A>G (p.Asp697Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251196 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2090A>G has been reported in the literature in at least one compound heterozygous individual affected with Pendred Syndrome (e.g. Sloan-Heggen_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 26969326). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.