ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.64C>T (p.Arg22Trp) (rs749030456)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573120 SCV000664650 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000607189 SCV000715014 likely benign not specified 2017-09-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000695216 SCV000823701 uncertain significance Tuberous sclerosis 1 2018-01-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 22 of the TSC1 protein (p.Arg22Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs749030456, ExAC 0.01%). This variant has not been reported in the literature in the germline of individuals with TSC1-related disease. ClinVar contains an entry for this variant (Variation ID: 417731). Experimental studies have shown that this missense change disrupts the formation of the TSC1-TSC2 complex and leads to hyperactivation of the mTOR kinase (PMID: 28215400). 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.
OMIM RCV000477710 SCV000564179 pathogenic Focal cortical dysplasia type II 2017-04-11 no assertion criteria provided literature only

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