ClinVar

Description

The p.Glu737Asp variant in SLC26A4 has been previously reported in four individu als with hearing loss, one of whom had no inner ear abnormalities. It was not re ported for the remaining three individuals whether or not inner ear abnormalitie s were present (Dai 2009, LMM unpublished data). All these individuals were hete rozygous for this variant and a second pathogenic variant was not identified. Th is variant has been identified in 17/111562 European chromosomes by the Genome A ggregation Database (gnomAD, http://http://gnomad.broadinstitute.org; dbSNP rs20 0664061); however this frequency is not high enough to rule out a pathogenic rol e. A functional study reported that the p.Glu737Asp variant, when expressed in X enopus oocytes, had a reduced rate of Cl(-)/HCO(3)(-) exchange (Dai 2009), thoug h this in vitro assay may not accurately represent biological function. Computat ional prediction tools and conservation analyses suggest that the Glu737Asp vari ant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Glu73 7Asp variant is uncertain.