ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2536G>A (p.Val846Ile)

gnomAD frequency: 0.00001  dbSNP: rs747774791
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620020 SCV000740254 uncertain significance Cardiovascular phenotype 2017-11-28 criteria provided, single submitter clinical testing The p.V846I variant (also known as c.2536G>A), located in coding exon 25 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 2536. The valine at codon 846 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, isoleucine is the reference amino acid in other 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.
Color Diagnostics, LLC DBA Color Health RCV001190207 SCV001357649 uncertain significance Cardiomyopathy 2023-04-20 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 846 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. This variant has been identified in 4/279436 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.
Invitae RCV002531868 SCV002956238 uncertain significance Hypertrophic cardiomyopathy 2023-06-29 criteria provided, single submitter clinical testing 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 tolerated. 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. ClinVar contains an entry for this variant (Variation ID: 520384). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is present in population databases (rs747774791, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 846 of the MYBPC3 protein (p.Val846Ile).

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