ClinVar Miner

Submissions for variant NM_145239.3(PRRT2):c.436C>A (p.Pro146Thr)

dbSNP: rs1900084663
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001839305 SCV002099291 uncertain significance Seizures, benign familial infantile, 2; Episodic kinesigenic dyskinesia 1; Infantile convulsions and choreoathetosis 2021-04-16 criteria provided, single submitter clinical testing The inherited heterozygous c.436C>A (p.Pro146Thr) variant identified in the PRRT2 gene has not been reported in affected individuals in the literature. The variant is absent from the gnomAD(v3) database suggesting it is not a common benign variant in the populations represented in that database. The affected residue is moderately conserved. In silico tools provide conflicting predictions about potential pathogenicity of this variant. Based on the available evidence, the inherited heterozygous c.436C>A (p.Pro146Thr) variant identified in the PRRT2 gene is reported as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002034711 SCV002219111 uncertain significance Episodic kinesigenic dyskinesia 2023-09-22 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRRT2 protein function. ClinVar contains an entry for this variant (Variation ID: 1342554). This variant has not been reported in the literature in individuals affected with PRRT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 146 of the PRRT2 protein (p.Pro146Thr).
GeneDx RCV004728838 SCV005333694 uncertain significance not provided 2023-06-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29132464)

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