ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1238A>G (p.Gln413Arg)

gnomAD frequency: 0.00001  dbSNP: rs142498437
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411469 SCV000485281 likely pathogenic Pendred syndrome 2016-01-14 criteria provided, single submitter clinical testing
Invitae RCV001216381 SCV001388177 pathogenic not provided 2023-10-18 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 413 of the SLC26A4 protein (p.Gln413Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with SLC26A4-related conditions (PMID: 20137612, 21961810, 23185506, 24248179, 25015771, 25266519, 25290043, 25372295, 26752218). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 370080). 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. Experimental studies have shown that this missense change affects SLC26A4 function (PMID: 26752218). This variant disrupts the p.Gln413 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 RCV000411469 SCV002026920 likely pathogenic Pendred syndrome 2021-09-05 criteria provided, single submitter clinical testing
University of Washington Center for Mendelian Genomics, University of Washington RCV001291348 SCV001479822 likely pathogenic Hearing loss, autosomal recessive no assertion criteria provided research

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