ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.1079C>T (p.Ala360Val) (rs786204474)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169123 SCV000220333 likely pathogenic Pendred syndrome 2014-05-21 criteria provided, single submitter literature only
Invitae RCV000808026 SCV000948110 pathogenic not provided 2019-07-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 360 of the SLC26A4 protein (p.Ala360Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed as homozygous or in combination with SLC26A4 pathogenic variants in several individuals affected with hearing loss (PMID: 17697873, 21961810, 23838540, 26252218, 26969326). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 188793). 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). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000808026 SCV001786324 pathogenic not provided 2020-06-15 criteria provided, single submitter clinical testing Published functional studies demonstrate this variant impairs SLC26A4 protein localization and function (Yuan et al., 2012); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32447495, 30275481, 31541171, 27771369, 26252218, 21154317, 21961810, 17697873, 23838540, 26969326, 23185506, 30842343)
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital RCV000770860 SCV000902367 likely pathogenic Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 2019-02-26 no assertion criteria provided case-control
Natera, Inc. RCV000169123 SCV001455808 pathogenic Pendred syndrome 2020-09-16 no assertion criteria provided clinical testing

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