ClinVar Miner

Submissions for variant NM_145239.3(PRRT2):c.647C>G (p.Pro216Arg)

dbSNP: rs76335820
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001719806 SCV000242395 likely benign not provided 2021-03-27 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 20301633, 25502464, 23190448, 26598493, 31124310, 31154286)
Labcorp Genetics (formerly Invitae), Labcorp RCV000791448 SCV000820972 likely benign Episodic kinesigenic dyskinesia 2024-10-28 criteria provided, single submitter clinical testing
Mendelics RCV000055990 SCV001140085 likely benign Episodic kinesigenic dyskinesia 1 2019-05-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV001332952 SCV001525398 uncertain significance Infantile convulsions and choreoathetosis 2019-03-01 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002354247 SCV002656047 likely benign Inborn genetic diseases 2024-02-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005055555 SCV005727229 uncertain significance not specified 2024-11-04 criteria provided, single submitter clinical testing Variant summary: PRRT2 c.647C>G (p.Pro216Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 217286 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in PRRT2 causing Episodic Kinesigenic Dyskinesia 1, allowing no conclusion about variant significance. c.647C>G has been reported in the literature in individuals affected with Episodic Kinesigenic Dyskinesia, without strong evidence for causality (Liu _2013). These report(s) do not provide unequivocal conclusions about association of the variant with Episodic Kinesigenic Dyskinesia 1. Co-occurrences with other pathogenic variant(s) have been reported (PRRT2 c.510dup, p.Leu171SerfsX3), providing supporting evidence for a benign role (Liu _2013). At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Zhao_2019). ClinVar contains an entry for this variant (Variation ID: 65757). Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneReviews RCV000055990 SCV000087044 not provided Episodic kinesigenic dyskinesia 1 no assertion provided literature only

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