ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1024G>A (p.Val342Ile)

gnomAD frequency: 0.00001  dbSNP: rs397515882
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035365 SCV000059013 likely benign not specified 2012-08-10 criteria provided, single submitter clinical testing Val342Ile in exon 12 of MYBPC3: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including several mamma ls and evolutionarily distant species that carry an isoleucine (Ile; this varian t) at this position despite high nearby amino acid conservation. In addition, co mputational analyses (AlignGVGD, PolyPhen2, SIFT) do not suggest a high likeliho od of impact to the protein.
Invitae RCV000794480 SCV000933892 uncertain significance Hypertrophic cardiomyopathy 2023-08-23 criteria provided, single submitter clinical testing 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. 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 isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 42500). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is present in population databases (rs397515882, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 342 of the MYBPC3 protein (p.Val342Ile).
Color Diagnostics, LLC DBA Color Health RCV003531908 SCV004358752 uncertain significance Cardiomyopathy 2022-12-05 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 342 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 an individual affected with hypertrophic cardiomyopathy (PMID: 25611685). This variant has been identified in 3/248712 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.

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