ClinVar Miner

Submissions for variant NM_003106.4(SOX2):c.254C>T (p.Thr85Met)

gnomAD frequency: 0.00001  dbSNP: rs1007978252
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001732531 SCV001982722 likely benign not provided 2021-11-29 criteria provided, single submitter clinical testing In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV005057555 SCV005711777 uncertain significance Anophthalmia/microphthalmia-esophageal atresia syndrome 2024-02-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 85 of the SOX2 protein (p.Thr85Met). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SOX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1300618). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SOX2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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