ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12705C>T (p.Phe4235=) (rs373606009)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036673 SCV000060328 likely benign not specified 2012-01-10 criteria provided, single submitter clinical testing Phe4235Phe in exon 90 of RYR2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. This variant has been identified in 0.06% (4/ 6706) of European American chromosomes from a broad, though clinically unspecifi ed population (NHLBI Exome Sequencing Project; . Phe4235Phe in exon 90 of RYR2 (NHLBI Exome Sequencing Project; allele frequ ency = 0.06%, 4/6706)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724635 SCV000233207 uncertain significance not provided 2015-03-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620335 SCV000736861 likely benign Cardiovascular phenotype 2017-07-10 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV001081670 SCV000760726 likely benign Catecholaminergic polymorphic ventricular tachycardia 2020-11-21 criteria provided, single submitter clinical testing
Color Health, Inc RCV000777965 SCV000914066 benign Cardiomyopathy 2018-10-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000036673 SCV000920169 benign not specified 2018-10-01 criteria provided, single submitter clinical testing Variant summary: RYR2 c.12705C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00034 in 276036 control chromosomes. The observed variant frequency is approximately 14 fold of the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.12705C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as benign.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000777965 SCV001333071 likely benign Cardiomyopathy 2017-12-11 criteria provided, single submitter clinical testing

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