ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5143A>G (p.Met1715Val)

dbSNP: rs397514974
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569125 SCV000675728 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-05 criteria provided, single submitter clinical testing The p.M1715V variant (also known as c.5143A>G), located in coding exon 39 of the TSC2 gene, results from an A to G substitution at nucleotide position 5143. The methionine at codon 1715 is replaced by valine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001071078 SCV001236363 uncertain significance Tuberous sclerosis 2 2024-06-17 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1715 of the TSC2 protein (p.Met1715Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of TSC2-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 64967). 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.
Genome-Nilou Lab RCV001071078 SCV002040871 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000055170 SCV004817510 uncertain significance Tuberous sclerosis syndrome 2023-05-16 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 1715 of the TSC2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Tuberous sclerosis database (TSC2) RCV000055170 SCV000083388 not provided Tuberous sclerosis syndrome no assertion provided curation

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