ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.950C>T (p.Thr317Ile)

dbSNP: rs1596289105
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817306 SCV000957858 uncertain significance Tuberous sclerosis 2 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 317 of the TSC2 protein (p.Thr317Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 660174). 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 TSC2 protein function with a negative predictive value of 95%. 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.
GeneDx RCV002298787 SCV002588355 uncertain significance not provided 2022-04-28 criteria provided, single submitter clinical testing 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18466115)
Ambry Genetics RCV002372313 SCV002688416 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-04 criteria provided, single submitter clinical testing The p.T317I variant (also known as c.950C>T), located in coding exon 9 of the TSC2 gene, results from a C to T substitution at nucleotide position 950. The threonine at codon 317 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004803262 SCV005427059 uncertain significance Tuberous sclerosis syndrome 2024-08-06 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004735819 SCV005365737 uncertain significance TSC2-related disorder 2024-03-29 no assertion criteria provided clinical testing The TSC2 c.950C>T variant is predicted to result in the amino acid substitution p.Thr317Ile. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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