ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4142C>T (p.Pro1381Leu) (rs397515264)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000475654 SCV000544497 uncertain significance Tuberous sclerosis 2 2016-09-28 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1381 of the TSC2 protein (p.Pro1381Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs397515264, ExAC 0.002%). This variant has been reported in an individuals with suspected tuberous sclerosis complex (PMID: 22903760). ClinVar contains an entry for this variant (Variation ID: 65353). Experimental studies have shown that this missense change has no significant effect on TSC2 or TSC1 protein levels, or the ability of the TSC complex to inhibit TORC1 kinase in vitro (PMID: 22903760). In summary, this variant is a rare missense change that does not affect protein function in vitro. It has been reported in both the population and an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Tuberous sclerosis database (TSC2) RCV000055577 SCV000083801 not provided Tuberous sclerosis syndrome no assertion provided curation

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