ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4927A>C (p.Asn1643His) (rs45517379)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478359 SCV000568295 pathogenic not provided 2017-03-22 criteria provided, single submitter clinical testing The N1643H variant in the TSC2 gene has been reported previously in an individual with a clinical diagnosis of TSC (Dabora et al., 2001). Functional studies indicate that N1643H disrupts the TSC1–TSC2 complex (Hoogeveen-Westerveld et al. 2011). The N1643H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N1643H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Additionally, multiple missense variants at the same position (N1643I, N1643S, N1643K) as well as multiple missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with TSC (Stenson et al., 2014), supporting the functional importance of this region of the protein.
Tuberous sclerosis database (TSC2) RCV000043177 SCV000066977 not provided Tuberous sclerosis syndrome no assertion provided curation

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