ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1541A>G (p.Gln514Arg)

gnomAD frequency: 0.00006  dbSNP: rs111033316
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000320959 SCV000329521 pathogenic not provided 2021-02-01 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect; L90P interferes with proper localization of the SLC26A4 protein (Choi et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26969326, 15689455, 19204907, 25394566, 19318451, 23555729)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507599 SCV000605151 pathogenic not specified 2017-03-02 criteria provided, single submitter clinical testing
Invitae RCV000320959 SCV001225432 pathogenic not provided 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 514 of the SLC26A4 protein (p.Gln514Arg). This variant is present in population databases (rs111033316, gnomAD 0.01%). This missense change has been observed in individuals with Pendred syndrome (PMID: 15689455, 25394566, 26969326). ClinVar contains an entry for this variant (Variation ID: 43511). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC26A4 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SLC26A4 function (PMID: 19204907). This variant disrupts the p.Gln514 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18285825, 19017801). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000666548 SCV002026938 pathogenic Pendred syndrome 2021-09-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV003473266 SCV004201841 pathogenic Autosomal recessive nonsyndromic hearing loss 4 2023-10-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036445 SCV000060100 likely pathogenic Rare genetic deafness 2009-06-03 no assertion criteria provided clinical testing
Counsyl RCV000666548 SCV000790855 likely pathogenic Pendred syndrome 2017-04-12 no assertion criteria provided clinical testing

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