Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002525643 | SCV000554605 | likely benign | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-12-30 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000617414 | SCV000737661 | likely benign | Cardiovascular phenotype | 2021-02-23 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Center for Advanced Laboratory Medicine, |
RCV000852598 | SCV000995301 | likely benign | Cardiomyopathy | 2017-09-08 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174899 | SCV001338326 | likely benign | not specified | 2020-02-24 | criteria provided, single submitter | clinical testing | Variant summary: RYR2 c.13672C>T (p.His4558Tyr) results in a conservative amino acid change located in the Ryanodine Receptor TM 4-6 domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00024 in 249268 control chromosomes, predominantly at a frequency of 0.0017 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 28 fold of the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Arrhythmia phenotype (6e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. In the literature, the variant was detected in a patient with Catecholaminergic Polymorphic Ventricular Tachycardia who had other environmental risk factors (Diffley_2012), but has not been reported in other affected individuals via publications or databases. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, two as likely benign and one as VUS. Based on the evidence outlined above, the variant was classified as likely benign. |
| Color Diagnostics, |
RCV000852598 | SCV001356136 | likely benign | Cardiomyopathy | 2018-12-18 | criteria provided, single submitter | clinical testing |