ClinVar Miner

Submissions for variant NM_145239.3(PRRT2):c.431C>T (p.Pro144Leu) (rs1317648011)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523548 SCV000620037 uncertain significance not provided 2017-08-21 criteria provided, single submitter clinical testing The P144L variant in the PRRT2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P144L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. e interpret P144L as a variant of uncertain significance.
Invitae RCV000542218 SCV000645427 uncertain significance Episodic kinesigenic dyskinesia 1 2017-05-02 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 144 of the PRRT2 protein (p.Pro144Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PRRT2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; 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. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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