ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3430G>T (p.Val1144Leu) (rs45517294)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001020293 SCV001181749 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-29 criteria provided, single submitter clinical testing The p.V1144L variant (also known as c.3430G>T), located in coding exon 29 of the TSC2 gene, results from a G to T substitution at nucleotide position 3430. This variant behaved like wildtype and was classified as "probably neutral" in an cell-based kinase assay (Hoogeveen-Westerveld M et al. Hum. Mutat. 2013 Jan;34(1):167-75). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001057920 SCV001222446 uncertain significance Tuberous sclerosis 2 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 1144 of the TSC2 protein (p.Val1144Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in one individual suspected to be affected with tuberous sclerosis (PMID: 22903760). ClinVar contains an entry for this variant (Variation ID: 49259). One experimental study has shown that this missense change does not have an effect on protein function in vitro (PMID: 22903760). In summary, this variant is a rare missense change that has shown a neutral effect on protein function. However, the evidence is insufficient at this point to classify it conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Tuberous sclerosis database (TSC2) RCV000042518 SCV000066309 not provided Tuberous sclerosis syndrome no assertion provided curation

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