ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3673G>A (p.Ala1225Thr)

gnomAD frequency: 0.00001  dbSNP: rs1278226452
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788686 SCV000927883 uncertain significance not provided 2018-08-27 criteria provided, single submitter clinical testing
Invitae RCV000798034 SCV000937627 uncertain significance Hypertrophic cardiomyopathy 2024-01-25 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 1225 of the MYBPC3 protein (p.Ala1225Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of MYBPC3-related conditions (PMID: 32815737, 32880476). ClinVar contains an entry for this variant (Variation ID: 636766). 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.
Color Diagnostics, LLC DBA Color Health RCV001177783 SCV001342049 uncertain significance Cardiomyopathy 2023-07-27 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 1225 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 individuals affected with hypertrophic cardiomyopathy (PMID: 32815737, 32880476). This variant has been identified in 1/249216 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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