ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1009G>A (p.Ala337Thr)

gnomAD frequency: 0.00001  dbSNP: rs769830766
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001182776 SCV001348341 uncertain significance Cardiomyopathy 2023-01-27 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 337 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 dilated cardiomyopathy (PMID: 28416588). This variant has been identified in 1/279410 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.
GeneDx RCV002286817 SCV002577268 uncertain significance not provided 2022-03-26 criteria provided, single submitter clinical testing Reported in association with dilated cardiomyopathy (Dal Ferro et al., 2017); however, specific clinical information was not provided; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28416588, 31514951)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001182776 SCV003838285 uncertain significance Cardiomyopathy 2022-03-22 criteria provided, single submitter clinical testing
Invitae RCV003586282 SCV004294815 uncertain significance Hypertrophic cardiomyopathy 2023-10-04 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 337 of the MYBPC3 protein (p.Ala337Thr). This variant is present in population databases (rs769830766, gnomAD 0.0008%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 28416588, 31514951). ClinVar contains an entry for this variant (Variation ID: 922609). 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 disruptive. 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.

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