ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1298C>G (p.Ser433Cys)

dbSNP: rs397515187
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000475576 SCV000544437 benign Tuberous sclerosis 2 2024-08-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV001010823 SCV001171075 likely benign Hereditary cancer-predisposing syndrome 2020-09-03 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 RCV000475576 SCV002041147 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001010823 SCV002532766 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-05 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV000055478 SCV004819248 uncertain significance Tuberous sclerosis syndrome 2024-09-23 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 433 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). A functional study has shown that this variant did not affect TSC1/TSC2 interaction or activation of mTORC1 (PMID: 22903760). This variant has been reported in an individual with suspected tuberous sclerosis complex (PMID: 22903760). This variant has not been identified 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) RCV000055478 SCV000083699 not provided Tuberous sclerosis syndrome no assertion provided curation

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