ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.488T>C (p.Phe163Ser)

dbSNP: rs1596270677
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820781 SCV000961508 uncertain significance Tuberous sclerosis 2 2021-07-22 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 163 of the TSC2 protein (p.Phe163Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine.
GeneDx RCV001585759 SCV001812490 likely pathogenic not provided 2023-07-18 criteria provided, single submitter clinical testing Reported as heterozygous in astrocytic tumor cells from individual with TSC in published literature (Yang et al., 2016); Functional studies demonstrate a damaging effect on activity of the TSC complex (Ekong, 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27516388, 18466115, 26703369)
Genome-Nilou Lab RCV000820781 SCV002040550 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000820781 SCV004698062 uncertain significance Tuberous sclerosis 2 2024-02-08 criteria provided, single submitter clinical testing Criteria applied: PS4_SUP,PM2_SUP,PP3

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