ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4142C>T (p.Pro1381Leu)

dbSNP: rs397515264
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000475654 SCV000544497 benign Tuberous sclerosis 2 2023-07-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV003162432 SCV003870174 likely benign Hereditary cancer-predisposing syndrome 2023-02-02 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.
All of Us Research Program, National Institutes of Health RCV000055577 SCV004817489 uncertain significance Tuberous sclerosis syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 1381 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). A functional study demonstrated no effect on TSC1 or TSC2 protein abundance, or on TSC1-TSC2 dependent inhibition of TORC1 activity (PMID: 22903760). This variant has been reported in an individual with suspected tuberous sclerosis complex (PMID: 22903760). This variant has been identified in 1/248882 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) RCV000055577 SCV000083801 not provided Tuberous sclerosis syndrome no assertion provided curation

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