ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.1802C>T (p.Pro601Leu) (rs543077026)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000606429 SCV000726583 likely benign not specified 2018-02-20 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 RCV000641985 SCV000763637 uncertain significance Tuberous sclerosis 1 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 601 of the TSC1 protein (p.Pro601Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs543077026, ExAC 0.01%). This variant has not been reported in the literature in individuals with TSC1-related disease. 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 leucine 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.

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