ClinVar Miner

Submissions for variant NM_001134363.3(RBM20):c.448G>A (p.Ala150Thr) (rs199868951)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036993 SCV000060649 likely benign not specified 2012-12-11 criteria provided, single submitter clinical testing Ala150Thr in exon 2 of RBM20: This variant is not expected to have clinical sign ificance due to a lack of conservation across species, including mammals. Of not e, 14 mammals have a Threonine (Thr; this variant) at this position despite high nearby amino acid conservation. In addition, computational analyses (AlignGVGD, PolyPhen2, SIFT) do not suggest a high likelihood of impact to the protein. In addition, this variant has been identified in 3/3182 European American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS).
GeneDx RCV000036993 SCV000236303 benign not specified 2018-01-16 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.
Illumina Clinical Services Laboratory,Illumina RCV000469728 SCV000360334 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 RCV000469728 SCV000562784 benign Dilated cardiomyopathy 1DD 2020-12-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618530 SCV000736050 benign Cardiovascular phenotype 2016-10-19 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 RCV000770272 SCV000901704 likely benign Cardiomyopathy 2017-06-08 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852627 SCV000995331 benign Familial dilated cardiomyopathy and peripheral neuropathy 2019-06-03 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000036993 SCV000280435 uncertain significance not specified 2013-01-26 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Ala150Thr (c.448 G>A, A150T) in the RBM20 gene The variant has not been reported in association with disease. In silico analysis with PolyPhen-2 predicts the variant to be benign. The alanine at codon 150 is not conserved across species, and is in fact a threonine in some species, including mammals. Mutation taster predicts the variant to be benign. In total the variant has not been seen in 5 of ~2,579 published controls and individuals from publicly available population datasets. The variant is reported online in 3 of 1591 Caucasian individuals and 1 of 692 African-American individuals in the NHLBI Exome Sequencing Project dataset (as of January 27th, 2013). The phenotype of those individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension. The variant is listed in dbSNP (rs199868951), which refers to the NHLBI data and data from ClinSeq. In ClinSeq it was observed in 1 of 296 individuals; this cohort approximates a general population sample (with respect to Mendelian disease). It is listed in 1000 genomes but only in reference to the dbSNP entry (as of January 27th, 2013).

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