ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.2090A>C (p.Asp697Ala)

dbSNP: rs111033443
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036471 SCV000060126 uncertain significance not specified 2009-08-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852761 SCV002114439 likely pathogenic not provided 2024-05-29 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 697 of the SLC26A4 protein (p.Asp697Ala). This variant is present in population databases (rs111033443, gnomAD 0.0009%). This missense change has been observed in individual(s) with deafness and/or Pendred syndrome (PMID: 19509082, 25394566; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 43536). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SLC26A4 function (PMID: 19509082). This variant disrupts the p.Asp697 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been observed in individuals with SLC26A4-related conditions (PMID: 26969326), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV001852761 SCV005874610 pathogenic not provided 2024-08-26 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on protein function (PMID: 19509082); Observed with no second SLC26A4 variant in a patient with hearing loss in published literature (PMID: 19509082); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30245029, 19509082, 25394566)
Natera, Inc. RCV001826556 SCV002080023 uncertain significance Pendred syndrome 2021-03-22 no assertion criteria provided clinical testing

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