ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13573_13575TCT[1] (p.Ser4526del) (rs749495172)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619260 SCV000738017 uncertain significance Cardiovascular phenotype 2017-06-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000493000 SCV000583371 uncertain significance not specified 2017-05-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RYR2 gene. The c.13576_13578delTCT variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.13576_13578delTCT variant results in the in-frame deletion of a serine (S) residue at a position 4526 in the RYR2 gene, denoted p.Ser4526del. This deletion occurs at a position that is conserved in mammals and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, the c.13576_13578delTCT variant is 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). Nevertheless, this variant has not been observed in a significant number of affected individuals and it lacks both segregation and functional studies which would further clarify its pathogenicity.

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