Submissions for variant NM_001035.3(RYR2):c.12583G>A (p.Asp4195Asn)

dbSNP: rs794728791

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182825	SCV000235211	likely pathogenic	not provided	2013-08-14	criteria provided, single submitter	clinical testing	p.Asp4195Asn (GAC>AAC): c.12583 G>A in exon 90 of the RYR2 gene (NM_001035.2). The Asp4195Asn variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Asp4195Asn results in a semi-conservative amino acid substitution of negatively charged Aspartic acid with a neutral, polar Asparagine at a position that is conserved across species. In silico analysis predicts Asp4195Asn is damaging to the protein structure/function. Mutations in nearby residues (Glu4187Gln, Leu4188Pro, Thr4196Ala, Gln4201Arg) have been reported in association with arrhythmia, further supporting the functional importance of this region of the protein. Furthermore, the Asp4195Asn variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, while Asp4195Asn 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).