ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12648G>A (p.Ala4216=) (rs781557399)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000587919 SCV000697605 benign not provided 2017-01-09 criteria provided, single submitter clinical testing Variant summary: The RYR2 c.12648G>A (p.Ala4216Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 6/120450 control chromosomes, exclusively observed in the East Asian subpopulation at a frequency of 0.0006975 (6/8602). This frequency is about 28 times the estimated maximal expected allele frequency of a pathogenic RYR2 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. The variant of interest has not, to our knowledge, been reported as germline mutation in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Ambry Genetics RCV000617652 SCV000737893 likely benign Cardiovascular phenotype 2017-01-31 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV000639168 SCV000760734 likely benign Catecholaminergic polymorphic ventricular tachycardia 2017-11-10 criteria provided, single submitter clinical testing
Color RCV001185316 SCV001351504 likely benign Cardiomyopathy 2019-12-09 criteria provided, single submitter clinical testing

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