ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1373G>A (p.Arg458Gln)

gnomAD frequency: 0.00001  dbSNP: rs878854077
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000231211 SCV000285240 likely benign Tuberous sclerosis 2 2025-02-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765262 SCV000896515 uncertain significance Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011245 SCV001171544 likely benign Hereditary cancer-predisposing syndrome 2023-11-18 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 RCV001589172 SCV001822580 uncertain significance not provided 2024-02-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Identified in a cohort of patients with Cowden syndrome or Bannayan-Riley-Ruvalcaba syndrome without identifiable PTEN variants (PMID: 29684080); This variant is associated with the following publications: (PMID: 27994516, 29684080)
Genome-Nilou Lab RCV000231211 SCV002039545 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000231211 SCV003821604 uncertain significance Tuberous sclerosis 2 2019-05-01 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998801 SCV004819264 uncertain significance Tuberous sclerosis syndrome 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 458 of the TSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 1/155654 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.

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