ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4868C>T (p.Thr1623Ile) (rs397515220)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413607 SCV000490980 likely pathogenic not provided 2015-12-29 criteria provided, single submitter clinical testing The T1623I variant in the TSC2 gene has previously been reported in a patient with suspected tuberous sclerosis complex (TSC) (Hoogeveen-Westerveld et al., 2013). Functional studies have shown that T1623I results in a significant reduction of TSC2 signal (Hoogeveen-Westerveld et al., 2013). The T1623I variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T1623I 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. This substitution occurs at a position that is conserved across species. In silicoanalysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (H1620R, H1620Y, F1619S, L1624P) have been reported in the Human Gene Mutation Database inassociation with tuberous sclerosis (Stenson et al., 2014), supporting the functional importance of this region of the protein. The T1623I variant is a strong candidate for a pathogenic variant. However, the possibility it may be a rare benign variant cannot be excluded
Tuberous sclerosis database (TSC2) RCV000055523 SCV000083746 not provided Tuberous sclerosis syndrome no assertion provided curation

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