ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2273C>G (p.Ser758Cys)

gnomAD frequency: 0.00001  dbSNP: rs45517223
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000230681 SCV000285286 likely benign Tuberous sclerosis 2 2024-12-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV002315685 SCV000848454 likely benign Hereditary cancer-predisposing syndrome 2021-12-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome-Nilou Lab RCV000230681 SCV002039634 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV002261015 SCV002541302 uncertain significance not provided 2021-12-06 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998813 SCV004826512 uncertain significance Tuberous sclerosis syndrome 2023-11-02 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 758 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 tuberous sclerosis complex in the literature. This variant has been identified in 8/251070 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV002261015 SCV005625992 uncertain significance not provided 2024-10-29 criteria provided, single submitter clinical testing The TSC2 c.2273C>G (p.Ser758Cys) variant has not been reported in individuals with TSC2-related conditions in the published literature. The frequency of this variant in the general population, 0.00023 (8/34582 chromosomes in Admixed American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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