ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.437C>T (p.Thr146Ile)

gnomAD frequency: 0.00003  dbSNP: rs780458215
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176742 SCV001340785 uncertain significance Cardiomyopathy 2020-01-15 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 146 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 5/167712 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 RCV002559701 SCV002961957 uncertain significance Hypertrophic cardiomyopathy 2022-08-29 criteria provided, single submitter clinical testing The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 918905). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 146 of the MYBPC3 protein (p.Thr146Ile).
All of Us Research Program, National Institutes of Health RCV002559701 SCV004834790 uncertain significance Hypertrophic cardiomyopathy 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 146 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 5/167712 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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