ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.416G>T (p.Gly139Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001378586 SCV001576188 likely pathogenic not provided 2020-09-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 139 of the SLC26A4 protein (p.Gly139Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs756272252, ExAC 0.03%). This variant has been observed in individual(s) with clinical features of Pendred syndrome (PMID: 19287372, 23918157, 25317404). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Gly139 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been observed in individuals with SLC26A4-related conditions (PMID: 9618166), 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.
University of Washington Center for Mendelian Genomics, University of Washington RCV001291245 SCV001479670 likely pathogenic Autosomal recessive nonsyndromic deafness no assertion criteria provided research

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