ClinVar Miner

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

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Total submissions: 10
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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 2015-11-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (benign),Insufficient or conflicting evidence
Illumina Clinical Services Laboratory,Illumina RCV000321873 SCV000372346 uncertain significance Left ventricular noncompaction cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000378760 SCV000372347 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000267890 SCV000372348 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000267890 SCV000546490 uncertain significance Hypertrophic cardiomyopathy 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 574 of the MYBPC3 protein (p.Arg574Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs397515922, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with MYBPC3-related disease. ClinVar contains an entry for this variant (Variation ID: 42562). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000035429 SCV000616974 uncertain significance not specified 2017-03-02 criteria provided, single submitter clinical testing The R574Q variant of uncertain significance in the MYBPC3 gene has not been published as pathogenic or been reported as benign to our knowledge. It was not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although the R574Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties, this substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. Finally, two of three in silico prediction algorithms predict this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
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
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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