ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.2254G>A (p.Val752Ile)

dbSNP: rs765643529
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001235826 SCV001408531 uncertain significance Tuberous sclerosis 1 2019-09-19 criteria provided, single submitter clinical testing 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 isoleucine 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, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with TSC1-related conditions. This variant is present in population databases (rs765643529, ExAC 0.006%). This sequence change replaces valine with isoleucine at codon 752 of the TSC1 protein (p.Val752Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine.
Ambry Genetics RCV003166459 SCV003911757 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-12 criteria provided, single submitter clinical testing The p.V752I variant (also known as c.2254G>A), located in coding exon 16 of the TSC1 gene, results from a G to A substitution at nucleotide position 2254. The valine at codon 752 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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