ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4571C>T (p.Ser1524Leu)

dbSNP: rs1441428144
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001864509 SCV002146716 uncertain significance Tuberous sclerosis 2 2024-04-29 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1524 of the TSC2 protein (p.Ser1524Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 1371331). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV002334775 SCV002637426 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-13 criteria provided, single submitter clinical testing The p.S1524L variant (also known as c.4571C>T), located in coding exon 35 of the TSC2 gene, results from a C to T substitution at nucleotide position 4571. The serine at codon 1524 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. 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.
All of Us Research Program, National Institutes of Health RCV004009235 SCV004840713 uncertain significance Tuberous sclerosis syndrome 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces serine with leucine at codon 1524 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 1/249800 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.

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