ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.754T>C (p.Phe252Leu)

dbSNP: rs1565630281
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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 RCV000770380 SCV000901821 uncertain significance Cardiomyopathy 2017-09-18 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000845301 SCV000987337 uncertain significance Primary familial hypertrophic cardiomyopathy criteria provided, single submitter clinical testing
Invitae RCV002533960 SCV003321929 uncertain significance Hypertrophic cardiomyopathy 2022-05-11 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 252 of the MYBPC3 protein (p.Phe252Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 33782553; Invitae). ClinVar contains an entry for this variant (Variation ID: 626782). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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 RCV000770380 SCV004358769 uncertain significance Cardiomyopathy 2022-03-24 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with leucine at codon 252 of the MYBPC3 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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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