Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037003 | SCV000060659 | uncertain significance | not specified | 2017-12-08 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Gly284Arg var iant in RBM20 has been identified by our laboratory in 1 Caucasian adult with fe atures of DCM and ARVC. It has also been identified in 0.07% (53/71906) of Europ ean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadi nstitute.org; dbSNP rs201148126). Computational prediction tools and conservatio n analysis do not provide strong support for or against an impact to the protein . In summary, while the clinical significance of the p.Gly284Arg variant is unce rtain, its frequency suggests that it is more likely to be benign. ACMG/AMP Crit eria applied: BS1. |
| Gene |
RCV000766684 | SCV000236327 | uncertain significance | not provided | 2023-06-26 | criteria provided, single submitter | clinical testing | Reported in patients with cardiomyopathy and in one case of SIDS; however, some of these individuals harbored additional variants in cardiogenetic genes (Lopes et al., 2013; van Lint et al., 2019; Gaertner et al., 2020; Neubauer et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30847666, 32840935, 30871351, 28074886, 23396983) |
| Illumina Laboratory Services, |
RCV000458367 | SCV000360342 | uncertain significance | Dilated cardiomyopathy 1DD | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV000458367 | SCV000552927 | likely benign | Dilated cardiomyopathy 1DD | 2024-01-17 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000458367 | SCV000605013 | uncertain significance | Dilated cardiomyopathy 1DD | 2023-10-16 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000458367 | SCV000611431 | uncertain significance | Dilated cardiomyopathy 1DD | 2017-05-23 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000618197 | SCV000736694 | likely benign | Cardiovascular phenotype | 2021-04-19 | 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. |
| CHEO Genetics Diagnostic Laboratory, |
RCV001170719 | SCV001333322 | likely benign | Cardiomyopathy | 2023-02-21 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000037003 | SCV002103594 | likely benign | not specified | 2022-02-28 | criteria provided, single submitter | clinical testing | Variant summary: RBM20 c.850G>A (p.Gly284Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 153600 control chromosomes, predominantly at a frequency of 0.00079 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 17-fold of the estimated maximal expected allele frequency for a pathogenic variant in RBM20 causing Dilated Cardiomyopathy phenotype (4.7e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.850G>A has been reported in the literature in individuals affected with hypertrophic cardiomyopathy, sudden infant death syndrome and arrhythmogenic right ventricular cardiomyopathy (Lopes_2013, Neubauer_2017, van Lint_2019). These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. Co-occurrences with pathogenic variants have been reported (MYBPC3 c.1624+4A>T; MYBPC3 c.1624G>C, p.E542Q; Lopes_2013 and Internal testing), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely benign and eight ClinVar submitters (evaluation after 2014) cite it as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000766684 | SCV000925207 | uncertain significance | not provided | 2017-08-08 | no assertion criteria provided | provider interpretation |