ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2086T>C (p.Cys696Arg) (rs45483301)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000807899 SCV000947979 uncertain significance Tuberous sclerosis 2 2018-09-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 696 of the TSC2 protein (p.Cys696Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with tuberous sclerosis complex (PMID: 16981987, 14641237, 21510812). ClinVar contains an entry for this variant (Variation ID: 50105). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Cys696 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 10205261), which suggests that this may be a clinically significant amino acid residue. 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.
Tuberous sclerosis database (TSC2) RCV000043372 SCV000067178 not provided Tuberous sclerosis syndrome no assertion provided curation

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