ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.301G>A (p.Val101Met)

gnomAD frequency: 0.00001  dbSNP: rs878854089
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227019 SCV000285325 uncertain significance Tuberous sclerosis 2 2023-01-30 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 238006). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 101 of the TSC2 protein (p.Val101Met).
Ambry Genetics RCV000569350 SCV000675642 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-27 criteria provided, single submitter clinical testing The p.V101M variant (also known as c.301G>A), located in coding exon 3 of the TSC2 gene, results from a G to A substitution at nucleotide position 301. The valine at codon 101 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000227019 SCV002040536 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
GeneDx RCV002466476 SCV002762099 uncertain significance not provided 2022-06-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter 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)

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