ClinVar Miner

Submissions for variant NM_001134363.3(RBM20):c.1881-3C>T (rs138436392)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036951 SCV000060607 likely benign not specified 2012-08-16 criteria provided, single submitter clinical testing c.1881-3C>T in intron 8 of RBM20: This variant is not expected to have clinical significance because it has been identified in 1.8% (25/1380) of African America n chromosomes by the NHLBI Exome Sequencing Project ( u/EVS/; dbSNP rs138436392).
GeneDx RCV000036951 SCV000171317 benign not specified 2013-07-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000036951 SCV000233024 benign not specified 2014-05-26 criteria provided, single submitter clinical testing
Invitae RCV000232795 SCV000286185 benign Dilated cardiomyopathy 1DD 2020-12-06 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000036951 SCV000306790 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000248544 SCV000319105 benign Cardiovascular phenotype 2015-07-27 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769263 SCV000900639 benign Cardiomyopathy 2016-03-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000232795 SCV001159591 benign Dilated cardiomyopathy 1DD 2019-11-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000232795 SCV001262180 likely benign Dilated cardiomyopathy 1DD 2018-01-12 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000036951 SCV001338643 benign not specified 2020-04-13 criteria provided, single submitter clinical testing Variant summary: RBM20 c.1881-3C>T alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.001 in 146224 control chromosomes, predominantly at a frequency of 0.019 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 760- fold the estimated maximal expected allele frequency for a pathogenic variant in RBM20 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1881-3C>T has been reported in the literature in individuals affected with Cardiomyopathy (e.g. Pugh_2014). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000232795 SCV000732917 benign Dilated cardiomyopathy 1DD no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000036951 SCV001920860 benign not specified no assertion criteria provided clinical testing

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