ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.730T>C (p.Cys244Arg) (rs137854101)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478154 SCV000568289 pathogenic not provided 2017-02-17 criteria provided, single submitter clinical testing The C244R variant in the TSC2 gene was reported previously in a proband with TSC who also harbored two additional variants in the TSC2 gene; however phase was undetermined (Nellist et al,. 2008). The proband's mother presented with angiomyolipoma but no other features of TSC and was reported to harbor the two additional TSC2 variants identified in the proband; the origin of the C244R variant was unable to be determined (Nellist et al,. 2008). Functional studies of the C244R variant demonstrate reduced binding of the TSC2 protein to TSC1 (Nellist et al,. 2008; Hoogeveen-Westerveld et al., 2011). This substitution occurs at a position that is conserved across species, and missense variants in nearby residues (T246A) and at the same residue (C244Y) have been reported in the Human Gene Mutation Database in association with tuberous sclerosis complex (Stenson et al., 2014). The C244R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, the C244R variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, the presence of C244R is consistent with the diagnosis of tuberous sclerosis complex in this individual.
Tuberous sclerosis database (TSC2) RCV000043163 SCV000066962 not provided Tuberous sclerosis syndrome no assertion provided curation

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