ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3767C>T (p.Pro1256Leu)

dbSNP: rs1596400594
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000808252 SCV000948351 uncertain significance Tuberous sclerosis 2 2021-08-06 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TSC2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 1256 of the TSC2 protein (p.Pro1256Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine.
GeneDx RCV002279962 SCV002568783 uncertain significance not provided 2022-02-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002363082 SCV002625950 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-14 criteria provided, single submitter clinical testing The p.P1256L variant (also known as c.3767C>T), located in coding exon 30 of the TSC2 gene, results from a C to T substitution at nucleotide position 3767. The proline at codon 1256 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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