ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.676A>G (p.Ile226Val)

dbSNP: rs1336201335
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000770382 SCV000901823 uncertain significance Cardiomyopathy 2017-08-04 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000770382 SCV000907842 uncertain significance Cardiomyopathy 2018-10-04 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the Ig-like domain C1 of the MYBPC3 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/244368 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000792039 SCV000931311 uncertain significance Hypertrophic cardiomyopathy 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 226 of the MYBPC3 protein (p.Ile226Val). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 626784). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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.
Ambry Genetics RCV003380708 SCV004090579 uncertain significance Cardiovascular phenotype 2023-06-25 criteria provided, single submitter clinical testing The p.I226V variant (also known as c.676A>G), located in coding exon 6 of the MYBPC3 gene, results from an A to G substitution at nucleotide position 676. The isoleucine at codon 226 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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