ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.364G>A (p.Ala122Thr)

gnomAD frequency: 0.00001  dbSNP: rs754633960
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001187350 SCV001354124 uncertain significance Cardiomyopathy 2023-03-16 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 122 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 not been reported in individuals affected with MYBPC3-related disorders in the literature; it has been reported in a healthy control individual (PMID: 24510615). This variant has been identified in 2/164814 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.
Ambry Genetics RCV002451391 SCV002613849 uncertain significance Cardiovascular phenotype 2021-09-17 criteria provided, single submitter clinical testing The p.A122T variant (also known as c.364G>A), located in coding exon 3 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 364. The alanine at codon 122 is replaced by threonine, an amino acid with similar properties. This variant has been detected in a healthy control cohort; however, details were limited (Kapplinger JD et al. J Cardiovasc Transl Res, 2014 Apr;7:347-61). 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.
Invitae RCV003770097 SCV004612508 uncertain significance Hypertrophic cardiomyopathy 2023-12-21 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 122 of the MYBPC3 protein (p.Ala122Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 925424). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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.