Total submissions: 4
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. |
Gene |
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- |
RCV000820781 | SCV002040550 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000820781 | SCV004698062 | uncertain significance | Tuberous sclerosis 2 | 2024-02-08 | criteria provided, single submitter | clinical testing | Criteria applied: PS4_SUP,PM2_SUP,PP3 |