ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.934C>T (p.Leu312Phe)

dbSNP: rs755368431
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459830 SCV000544332 uncertain significance Tuberous sclerosis 2 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 312 of the TSC2 protein (p.Leu312Phe). 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: 405963). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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.
Ambry Genetics RCV000568871 SCV000675688 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-01 criteria provided, single submitter clinical testing The p.L312F variant (also known as c.934C>T), located in coding exon 9 of the TSC2 gene, results from a C to T substitution at nucleotide position 934. The leucine at codon 312 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Genome-Nilou Lab RCV000459830 SCV002040581 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing

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