ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4313G>A (p.Arg1438Gln) (rs45448791)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000543604 SCV000644523 uncertain significance Tuberous sclerosis 2 2019-07-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1438 of the TSC2 protein (p.Arg1438Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs45448791, ExAC 0.01%). This variant has been reported as de novo in an individual affected with tuberous sclerosis complex (PMID: 15121797). ClinVar contains an entry for this variant (Variation ID: 50124). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on TSC2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001022275 SCV001183990 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-19 criteria provided, single submitter clinical testing Insufficient evidence
Tuberous sclerosis database (TSC2) RCV000043391 SCV000067197 not provided Tuberous sclerosis syndrome no assertion provided curation

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