ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3580G>A (p.Ala1194Thr)

gnomAD frequency: 0.00004  dbSNP: rs397516026
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766735 SCV000568215 uncertain significance not provided 2017-04-03 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYBPC3 gene. The A1194T variant has previously been reported in two individuals with HCM and one case of sudden infant death syndrome (SIDS) (Richard et al., 2003; Brion et al., 2012; Walsh et al., 2017). It has also been observed in one other individual referred for cardiac genetic testing at GeneDx, although this individual harbored additional cardiogenetic variants and no segregation data are available. Nevertheless, the A1194T variant has not been observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Additionally, A1194T is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this variant has not been observed in a significant number of affected individuals and it lacks both segregation and functional studies which would further clarify its pathogenicity.
Invitae RCV000793831 SCV000933207 uncertain significance Hypertrophic cardiomyopathy 2023-11-10 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1194 of the MYBPC3 protein (p.Ala1194Thr). This variant is present in population databases (rs397516026, gnomAD 0.02%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 12707239, 22361390, 27532257). ClinVar contains an entry for this variant (Variation ID: 42723). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Color Diagnostics, LLC DBA Color Health RCV001185757 SCV001352034 uncertain significance Cardiomyopathy 2022-12-02 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 1194 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in three individuals affected with hypertrophic cardiomyopathy (PMID: 12707239, 18258667, 27532257) and an infant affected with sudden death (PMID: 22361390). This variant has been identified in 9/280378 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002490482 SCV002797001 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-10-29 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035598 SCV000059249 uncertain significance not specified 2009-11-05 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.