ClinVar Miner

Submissions for variant NM_006941.4(SOX10):c.323T>C (p.Met108Thr)

dbSNP: rs1932464492
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital RCV001290167 SCV001478224 pathogenic Waardenburg syndrome type 2E 2019-01-01 criteria provided, single submitter clinical testing
GeneDx RCV002245947 SCV002513662 uncertain significance not provided 2022-05-12 criteria provided, single submitter clinical testing Identified in individuals with Kallmann Syndrome, but additional evidence is needed to support association with disease (Pingault et al., 2103; Maione et al., 2016); Published functional studies suggest this variant results in impairment of protein function, however additional studies are needed to validate the functional effect of this variant (Pingault et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); 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: 23643381, 27616149, 32442410, 33442024)
Labcorp Genetics (formerly Invitae), Labcorp RCV002245947 SCV004300013 pathogenic not provided 2024-12-02 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 108 of the SOX10 protein (p.Met108Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of SOX10-related conditions (PMID: 23643381, 34142234; internal data). ClinVar contains an entry for this variant (Variation ID: 995929). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SOX10 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SOX10 function (PMID: 23643381). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004528449 SCV004110116 likely pathogenic SOX10-related disorder 2024-02-27 no assertion criteria provided clinical testing The SOX10 c.323T>C variant is predicted to result in the amino acid substitution p.Met108Thr. This variant has been reported in one patient with Waardenburg syndrome and two patients with Kallmann syndrome, with in vitro studies indicating this variant leads to loss of function (Pingault. 2013. PubMed ID: 23643381; Maione. 2016. PubMed ID: 27616149; Wang. 2021. PubMed ID: 34142234). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic.

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