ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4498G>A (p.Val1500Met)

dbSNP: rs397515167
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166370 SCV000217160 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-02 criteria provided, single submitter clinical testing The p.V1500M variant (also known as c.4498G>A), located in coding exon 34 of the TSC2 gene, results from a G to A substitution at nucleotide position 4498. The valine at codon 1500 is replaced by methionine, an amino acid with highly similar properties. In one functional study, this alteration was classified as probably neutral as it did not appear to impact inhibition of TORC1 (Hoogeveen-Westerveld M et al. Hum. Mutat., 2013 Jan;34:167-75). 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.
Athena Diagnostics RCV000518605 SCV000615911 uncertain significance not specified 2017-02-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000813618 SCV000953985 likely benign Tuberous sclerosis 2 2024-09-19 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000813618 SCV002040832 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000166370 SCV002533546 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-26 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV003996481 SCV004817499 uncertain significance Tuberous sclerosis syndrome 2023-07-19 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 1500 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). Functional studies demonstrated no effect on TSC1 or TSC2 protein abundance, or on TSC1-TSC2 dependent inhibition of TORC1 activity (PMID: 22903760). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250308 chromosomes 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) RCV000055449 SCV000083670 not provided Lymphangiomyomatosis; Tuberous sclerosis syndrome no assertion provided curation

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