ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1730T>C (p.Val577Ala)

gnomAD frequency: 0.00001  dbSNP: rs56017519
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000175011 SCV000226430 uncertain significance not provided 2015-01-22 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000415063 SCV000492633 uncertain significance Hearing impairment 2015-03-27 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001785491 SCV002027016 uncertain significance Autosomal recessive nonsyndromic hearing loss 4 2021-09-05 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001785490 SCV002027017 uncertain significance Pendred syndrome 2021-09-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003488425 SCV004241046 uncertain significance not specified 2023-12-13 criteria provided, single submitter clinical testing Variant summary: SLC26A4 c.1730T>C (p.Val577Ala) results in a non-conservative amino acid change located in the STAS domain of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251110 control chromosomes. c.1730T>C has been reported in the literature in individuals affected with suspected Pendred Syndrome and hearing loss (Tesolin_2021, Roesch_2018, Likar_2018). These reports do not provide unequivocal conclusions about association of the variant with Pendred Syndrome. A functional study with variant-transfected cells showed severe loss in ion transport function, complete retention in the ER and dramatic reduction of expression (Roesch_2018). The following publications have been ascertained in the context of this evaluation (PMID: 29293505, 29320412, 34680964). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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