ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.512_514del (p.Glu171del) (rs794728812)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182856 SCV000235244 likely pathogenic not provided 2017-02-07 criteria provided, single submitter clinical testing The c.512_514delAAG variant in the RYR2 gene has not been reported previously as a pathogenic variant or as a benign polymorphism, to our knowledge. The c.512_514delAAG variant results in a deletion of a single Glutamic acid residue in the N-terminal region of the protein, which is part of the conserved MIR domain. This region is one of the mutation hotspots of RYR2, and several pathogenic variants have been reported in neighboring codons (Pro164Ser, Arg169Gln, Arg176Gln, Val186Met) (Medeiros-Domingo A et al., 2009). The Glu171 residue is highly conserved throughout evolution, and in silico analysis predicts c.512_514delAAG to be damaging to the protein structure/function. Additionally, another in-frame deletion (p.Asn4736del) has been reported previously in association with CPVT (Medeiros-Domingo A et al., 2009). In summary, the c.512_514delAAG variant in the RYR2 gene is a good candidate for a pathogenic variant.

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