ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5189C>G (p.Ser1730Cys)

dbSNP: rs2091134565
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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 RCV001232921 SCV001405494 uncertain significance Tuberous sclerosis 2 2019-07-31 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. This sequence change replaces serine with cysteine at codon 1730 of the TSC2 protein (p.Ser1730Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TSC2-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").
Ambry Genetics RCV002339639 SCV002643748 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-31 criteria provided, single submitter clinical testing The p.S1730C variant (also known as c.5189C>G), located in coding exon 40 of the TSC2 gene, results from a C to G substitution at nucleotide position 5189. The serine at codon 1730 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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 RCV004004845 SCV004838276 uncertain significance Tuberous sclerosis syndrome 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 1730 of the TSC2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 not been identified 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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