ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2447C>T (p.Pro816Leu) (rs45517236)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000430436 SCV000520881 uncertain significance not provided 2018-10-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TSC2 gene. The P816L variant hasbeen reported previously in an individual with tuberous sclerosis complex (TSC); however, thisindividual also had another TSC2 variant identified (Gilbert et al., 1998). It was not observed inapproximately 6,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The P816Lvariant is a semi-conservative amino acid substitution, which may impact secondary proteinstructure as these residues differ in some properties. This substitution occurs at a position that isconserved across species, and in silico analysis predicts this variant is probably damaging to theprotein structure/function. However, this substitution does not occur within known functionaldomains of the tuberin protein, where many pathogenic missense variants have been identified(Northrup et al., 2011; Au et al., 2007). Therefore, based on the currently available information, itis unclear whether this variant is a pathogenic variant or a rare benign variant.
Tuberous sclerosis database (TSC2) RCV000043451 SCV000067259 not provided Tuberous sclerosis syndrome no assertion provided curation

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