ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.1178C>T (p.Thr393Ile)

gnomAD frequency: 0.00006  dbSNP: rs201452238
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000465751 SCV000518093 likely benign not provided 2022-05-12 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Labcorp Genetics (formerly Invitae), Labcorp RCV001079535 SCV000552347 likely benign Tuberous sclerosis 1 2023-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000576108 SCV000675355 likely benign Hereditary cancer-predisposing syndrome 2020-04-07 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.
Genome-Nilou Lab RCV001079535 SCV002040121 likely benign Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002481304 SCV002798736 likely benign Lymphangiomyomatosis; Tuberous sclerosis 1; Isolated focal cortical dysplasia type II 2022-04-26 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003996037 SCV004840477 uncertain significance Tuberous sclerosis syndrome 2024-05-09 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 393 of the TSC1 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). A functional study with the variant reported slightly elevated MTOR activity compared to wild-type TSC1 (PMID: 33071758). This variant has not been reported in individuals affected with tuberous sclerosis in the literature. This variant has been identified in 6/282146 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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