ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5126C>T (p.Pro1709Leu) (rs45517393)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693889 SCV000822311 pathogenic Tuberous sclerosis 2 2018-04-01 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1709 of the TSC2 protein (p.Pro1709Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported has been reported in several individuals with tuberous sclerosis complex (PMID: 8824881, 22867869, 11520734, 22903760), including a number of de novo observations (PMID: 11112665, 10732801). The variant in also known as c.5075 C>T (p.Pro1186Leu) and c.5075C>T (p.Pro1686Leu) in the literature. ClinVar contains an entry for this variant (Variation ID: 49929). Experimental studies have shown that this missense change increases the ratio of T389-phosphorylated to total S6K when comparing to wild-type TSC2, which corresponds to an increase in mTORC1 activity (PMID: 22903760). For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000043196 SCV000066997 not provided Tuberous sclerosis syndrome no assertion provided curation

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