ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.1054G>A (p.Val352Ile) (rs796053447)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189809 SCV000243458 likely benign not specified 2013-05-16 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000228527 SCV000284664 uncertain significance Tuberous sclerosis 1 2017-06-16 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 352 of the TSC1 protein (p.Val352Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a TSC1-related disease. ClinVar contains an entry for this variant (Variation ID: 207607). 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, this variant has uncertain impact on TSC1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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