ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3391A>G (p.Met1131Val)

gnomAD frequency: 0.00001  dbSNP: rs775639244
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000473877 SCV000544534 benign Tuberous sclerosis 2 2024-12-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV001020177 SCV001181620 likely benign Hereditary cancer-predisposing syndrome 2024-02-14 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV001584141 SCV001812798 uncertain significance not provided 2021-05-24 criteria provided, single submitter clinical testing 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
Genome-Nilou Lab RCV000473877 SCV002039745 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001020177 SCV002533393 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-18 criteria provided, single submitter curation
Baylor Genetics RCV003463869 SCV004205087 uncertain significance Isolated focal cortical dysplasia type II 2023-05-26 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000718 SCV004828326 uncertain significance Tuberous sclerosis syndrome 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 1131 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 TSC2-related disorders in the literature. This variant has been identified in 1/206530 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.
GenomeConnect, ClinGen RCV000509526 SCV000607013 not provided TSC2-related disorder no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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