ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.3896T>C (p.Ile1299Thr) (rs772551383)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000612033 SCV000713842 uncertain significance not specified 2018-01-22 criteria provided, single submitter clinical testing The p.Ile1299Thr variant in RYR2 has not been previously reported in individuals with cardiomyopathy, but has been identified in 6/24010 African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; rs772 551383). Computational prediction tools and conservation analysis suggest that t he p.Ile1299Thr variant may impact the protein, though this information is not p redictive enough to determine pathogenicity. In summary, the clinical significan ce of the p.Ile1299Thr variant is uncertain. ACMG/AMP Criteria applied: PP3.
Integrated Genetics/Laboratory Corporation of America RCV000612033 SCV000918166 uncertain significance not specified 2018-10-15 criteria provided, single submitter clinical testing Variant summary: RYR2 c.3896T>C (p.Ile1299Thr) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.5e-05 in 275658 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3896T>C in individuals affected with Catecholaminergic Polymorphic Ventricular Tachycardia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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