ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4766C>T (p.Pro1589Leu)

gnomAD frequency: 0.00001  dbSNP: rs373635516
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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 RCV000823493 SCV000964354 benign Tuberous sclerosis 2 2024-01-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV001023009 SCV001184818 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-27 criteria provided, single submitter clinical testing The p.P1589L variant (also known as c.4766C>T), located in coding exon 36 of the TSC2 gene, results from a C to T substitution at nucleotide position 4766. The proline at codon 1589 is replaced by leucine, an amino acid with similar properties. This alteration was identified in an individual with a chordoma (Yepes S et al. Cancers (Basel), 2021 May;13:). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000823493 SCV002040852 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000823493 SCV003821624 uncertain significance Tuberous sclerosis 2 2019-05-20 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004002855 SCV004822385 uncertain significance Tuberous sclerosis syndrome 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 1589 of the TSC2 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has been identified in 1/249862 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.
GeneDx RCV004723250 SCV005332530 uncertain significance not provided 2023-08-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with chordoma (Yepes et al., 2021); This variant is associated with the following publications: (PMID: 18466115, 34070849)

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