ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1721G>A (p.Arg574Gln) (rs397515922)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723941 SCV000226724 uncertain significance not provided 2014-05-26 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000208484 SCV000264028 uncertain significance Primary dilated cardiomyopathy 2015-01-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV000247360 SCV000320550 uncertain significance Cardiovascular phenotype 2020-08-05 criteria provided, single submitter clinical testing The p.R574Q variant (also known as c.1721G>A), located in coding exon 18 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 1721. The arginine at codon 574 is replaced by glutamine, an amino acid with highly similar properties. This variant was detected in an an exome sequencing cohort in an individual with a cardiomyopathy diagnosis based on health record; however, details were limited (Pottinger TD et al. J Am Heart Assoc, 2020 Feb;9:e013808). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Illumina Clinical Services Laboratory,Illumina RCV000321873 SCV000372346 benign Left ventricular noncompaction 10 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001094061 SCV000372348 uncertain significance Familial hypertrophic cardiomyopathy 4 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 RCV000267890 SCV000546490 likely benign Hypertrophic cardiomyopathy 2020-12-06 criteria provided, single submitter clinical testing
GeneDx RCV000723941 SCV000616974 uncertain significance not provided 2020-05-06 criteria provided, single submitter clinical testing Functional studies have demonstrated that R574Q does not result in a significant splicing defect (Ito et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar (ClinVar Variant ID# 42562; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 28679633)
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000624304 SCV000740354 uncertain significance Primary familial hypertrophic cardiomyopathy 2016-05-18 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170954 SCV001333609 uncertain significance Cardiomyopathy 2019-03-18 criteria provided, single submitter clinical testing
Color Health, Inc RCV001170954 SCV001347632 likely benign Cardiomyopathy 2020-02-13 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000035429 SCV000059077 uncertain significance not specified 2009-02-26 no assertion criteria provided clinical testing

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