ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3718C>T (p.Arg1240Cys) (rs137854353)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537246 SCV000644468 uncertain significance Tuberous sclerosis 2 2018-07-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1240 of the TSC2 protein (p.Arg1240Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs137854353, ExAC 0.002%). This variant has been observed in an individual in the Leiden Open-source Variation Database (PMID: 21520333). However, in that individual a pathogenic allele was also identified in TSC2, which suggests that this c.3718C>T variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 50015). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on TSC2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Tuberous sclerosis database (TSC2) RCV000043283 SCV000067085 not provided Tuberous sclerosis syndrome no assertion provided curation

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