ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.2161A>G (p.Thr721Ala)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuberg Centre For Genomic Medicine, NCGM RCV004764830 SCV005374785 likely pathogenic Pendred syndrome 2023-05-20 criteria provided, single submitter clinical testing The observed missense variant c.2161A>G(p.Thr721Ala) in the SLC26A4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is absent in the gnomAD Exomes. This variant is located in a mutational hot spot. A different amino acid change [c.2162C>T (p.Thr721Met)] at the same position has been previously reported as Pathogenic (Rajalakshmi K, et al., 2023). The amino acid Threonine at position 721 is changed to a Alanine changing protein sequence and it might alter its composition and physico- chemical properties. Multiple lines of computational evidence (Polyphen - Probably damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely pathogenic. The same variant has been detected in the sibling sample (NCGM ID- 30507801294).

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