ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2840T>C (p.Leu947Pro)

dbSNP: rs1555509447
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000534078 SCV000644385 uncertain significance Tuberous sclerosis 2 2023-02-14 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 947 of the TSC2 protein (p.Leu947Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 467974). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001755847 SCV001996483 uncertain significance not provided 2020-06-16 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV000534078 SCV002040726 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002438416 SCV002748485 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-02 criteria provided, single submitter clinical testing The p.L947P variant (also known as c.2840T>C), located in coding exon 25 of the TSC2 gene, results from a T to C substitution at nucleotide position 2840. The leucine at codon 947 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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