ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3875C>T (p.Ser1292Phe)

dbSNP: rs796053497
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558015 SCV000644481 uncertain significance Tuberous sclerosis 2 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1292 of the TSC2 protein (p.Ser1292Phe). 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: 468044). 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 with a negative predictive value of 95%. 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 RCV001021336 SCV001182939 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-18 criteria provided, single submitter clinical testing The p.S1292F variant (also known as c.3875C>T), located in coding exon 31 of the TSC2 gene, results from a C to T substitution at nucleotide position 3875. The serine at codon 1292 is replaced by phenylalanine, an amino acid with highly dissimilar 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 RCV000558015 SCV002040794 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002491058 SCV002787242 uncertain significance Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2021-07-11 criteria provided, single submitter clinical testing
GeneDx RCV003105952 SCV003761750 uncertain significance not provided 2022-07-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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