ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3404ACT[1] (p.Tyr1136del) (rs730880674)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766373 SCV000208337 uncertain significance not provided 2017-03-21 criteria provided, single submitter clinical testing The c.3407_3409delACT variant of uncertain significance in the MYBPC3 gene has been reported previously in two individuals with HCM; however, no detailed clinical or segregation data were provided (Sequeira et al., 2013; Murphy et al., 2016). This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This three nucleotide deletion results in elimination of a tyrosine residue at position 1136, and does not result in a shift in reading frame. Tyrosine at this position is conserved in mammals and in silio analysis predicts this deletion to be damaging to the protein structer/function. However, the c.3407_3409delACT variant lacks sufficient evidence, including observation in a significant number of affected inidividuals, segregation studies, and functional characterization, that would further clarify its potential pathogenicity.
Blueprint Genetics RCV000208115 SCV000264060 likely pathogenic Primary familial hypertrophic cardiomyopathy 2015-10-29 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000625071 SCV000743674 pathogenic Familial hypertrophic cardiomyopathy 4 2017-10-26 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000625071 SCV000745028 pathogenic Familial hypertrophic cardiomyopathy 4 2017-05-31 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000158402 SCV000748030 uncertain significance not specified 2017-06-12 criteria provided, single submitter clinical testing
Center for Human Genetics,University of Leuven RCV000768480 SCV000886771 likely pathogenic Hypertrophic cardiomyopathy 2018-10-31 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769307 SCV000900685 uncertain significance Cardiomyopathy 2017-01-24 criteria provided, single submitter clinical testing
Invitae RCV000768480 SCV000949788 uncertain significance Hypertrophic cardiomyopathy 2018-10-11 criteria provided, single submitter clinical testing This variant, c.3407_3409delACT, results in the deletion of 1 amino acid(s) of the MYBPC3 protein (p.Tyr1136del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individuals affected with hypertrophic cardiomyopathy (PMID: 23508784, 26914223). ClinVar contains an entry for this variant (Variation ID: 181102). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000766373 SCV001740806 pathogenic not provided no assertion criteria provided clinical testing

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