ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3989C>T (p.Thr1330Met)

gnomAD frequency: 0.00002  dbSNP: rs397515209
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001703964 SCV000243697 likely benign not provided 2021-04-07 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 22490766, 23514105)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000190025 SCV000540609 uncertain significance not specified 2016-10-20 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 proband with features of TSC and the unaffected parent of a child with autism. ClinVar: VUS by GeneDx (who report they have seen it on their epilepsy panel?)
Invitae RCV000458400 SCV000544529 benign Tuberous sclerosis 2 2024-01-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571810 SCV000664598 likely benign Hereditary cancer-predisposing syndrome 2021-04-01 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.
Illumina Laboratory Services, Illumina RCV000055604 SCV001274388 uncertain significance Tuberous sclerosis syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab RCV000458400 SCV002039804 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004542721 SCV004760105 likely benign TSC2-related disorder 2023-08-03 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
All of Us Research Program, National Institutes of Health RCV000055604 SCV004817488 uncertain significance Tuberous sclerosis syndrome 2024-01-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 1330 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 been reported in an individual affected with tuberous sclerosis complex (TSC; PMID: 22490766) but also in an unaffected individual (PMID: 23514105) . This variant has been identified in 10/276322 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) RCV000055507 SCV000083730 not provided Autism spectrum disorder no assertion provided curation
Tuberous sclerosis database (TSC2) RCV000055604 SCV000083829 not provided Tuberous sclerosis syndrome no assertion provided curation

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