ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.11959G>A (p.Glu3987Lys) (rs794728778)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182802 SCV000235188 likely pathogenic not provided 2019-01-15 criteria provided, single submitter clinical testing The E3987K likely pathogenic variant in the RYR2 gene has been reported in association with catecholaminergic polymorphic ventricular tachycardia (CPVT) (Avari Silva et al., 2016); however, specific clinical details and segregation information were not provided. Nevertheless, this variant has been observed as a de novo variant in a patient referred for arrhythmia genetic testing at GeneDx. The E3987K variant is not observed in large population cohorts (Lek et al., 2016). The E3987K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Finally, the E3987K variant is located located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009). In summary, E3987K in the RYR2 gene is interpreted as a likely pathogenic variant.

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