ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1554G>A (p.Met518Ile)

gnomAD frequency: 0.00001  dbSNP: rs372499440
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001177780 SCV001342046 uncertain significance Cardiomyopathy 2023-03-30 criteria provided, single submitter clinical testing This missense variant replaces methionine with isoleucine at codon 518 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 3/280606 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 RCV003586276 SCV004273195 uncertain significance Hypertrophic cardiomyopathy 2023-11-08 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 518 of the MYBPC3 protein (p.Met518Ile). This variant is present in population databases (rs372499440, gnomAD 0.002%). 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: 919544). 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.

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