ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2654C>T (p.Thr885Met)

gnomAD frequency: 0.00002  dbSNP: rs397515981
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701144 SCV000829928 uncertain significance Hypertrophic cardiomyopathy 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 885 of the MYBPC3 protein (p.Thr885Met). 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. This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 20624503, 21302287). ClinVar contains an entry for this variant (Variation ID: 42649). 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 RCV001177059 SCV001341186 uncertain significance Cardiomyopathy 2023-02-15 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 885 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: 20624503, 21302287, 27532257, 32481709). This variant has been identified in 6/228884 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 RCV001588844 SCV001823171 uncertain significance not provided 2022-03-22 criteria provided, single submitter clinical testing Identified in patients with hypertrophic cardiomyopathy (HCM) in the published literature (Millat et al., 2010; Roncarati et al., 2011; Walsh et al., 2017); 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: 27532257, 21302287, 20624503)
Fulgent Genetics, Fulgent Genetics RCV002482959 SCV002792223 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-09-28 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035518 SCV000059168 uncertain significance not specified 2008-03-01 no assertion criteria provided clinical testing

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