ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.170C>A (p.Ser57Ter)

gnomAD frequency: 0.00001  dbSNP: rs111033200
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001389157 SCV001590423 pathogenic not provided 2023-11-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser57*) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). This variant is present in population databases (rs111033200, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with deafness (PMID: 12676893, 25372295, 28964290). ClinVar contains an entry for this variant (Variation ID: 1075541). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001389157 SCV002020691 pathogenic not provided 2023-05-24 criteria provided, single submitter clinical testing
3billion RCV002250759 SCV002521044 pathogenic Autosomal recessive nonsyndromic hearing loss 4 2022-05-22 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. This variant has been reported as pathogenic more than twice (ClinVar: VCV001075541, PMID:12676893). It has been reported with an extremely low frequency in the gnomAD v2.1.1 (https://gnomad.broadinstitute.org/) dataset. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics RCV002250759 SCV004201865 pathogenic Autosomal recessive nonsyndromic hearing loss 4 2023-11-16 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017832 SCV004848760 pathogenic Rare genetic deafness 2022-08-26 criteria provided, single submitter clinical testing The p.Ser57X variant in SLC26A4 has been reported in 1 individual with hearing loss and was compound heterozygous with a second pathogenic variant (Park 2003 PMID: 12676893), and it was absent from large population databases. This nonsense variant leads to a premature termination codon at position 57, which is predicted to lead to a truncated or absent protein. Loss of function of SLC26A4 is an established disease mechanism for autosomal recessive Pendred syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Pendred syndrome. ACMG/AMP criteria applied: PVS1, PM3, PM2_Supporting.
Natera, Inc. RCV001831400 SCV002079965 pathogenic Pendred syndrome 2020-04-14 no assertion criteria provided clinical testing

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