ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.14159T>C (p.Leu4720Pro) (rs794728801)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182842 SCV000235230 likely pathogenic not provided 2012-07-05 criteria provided, single submitter clinical testing p.Leu4720Pro (CTC>CCC): c.14159 T>C in exon 99 of the RYR2 gene (NM_001035.2). The Leu4720Pro variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Leu4720Pro results in a semi-conservative amino acid substitution, resulting in the gain of a sterically constrained Proline residue at a position that is highly conserved across species. In silico analysis predicts Leu4720Pro is probably damaging to the protein structure/function. This variant occurs in a mutation hotspot region of the RYR2 gene (Medeiros-Domingo A et al., 2009). Furthermore, the NHLBI ESP Exome Variant Server reports Leu4720Pro was not observed in approximately 4,800 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In summary, while Leu4720Pro is a good candidate for a disease-causing mutation, we cannot unequivocally determine the clinical significance of this variant. The variant is found in CPVT panel(s).

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