ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.782A>G (p.Lys261Arg) (rs371225009)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232948 SCV000284737 uncertain significance Tuberous sclerosis 1 2016-03-08 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 261 of the TSC1 protein (p.Lys261Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs371225009, ExAC 0.06%) but has not been reported in the literature in individuals with a TSC1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000719387 SCV000850253 likely benign History of neurodevelopmental disorder 2018-01-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification

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