Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000035500 | SCV000059150 | pathogenic | Hypertrophic cardiomyopathy | 2011-05-26 | criteria provided, single submitter | clinical testing | The Tyr842fs variant has not been reported in the literature nor been previously detected in over 1,600 Caucasian probands tested by our laboratory. This varia nt meets our criteria for pathogenicity (http://pcpgm.partners.org/LMM) based on the following data. This individual?s racial background is reported to be Cauca sian and the low frequency of this variant in this population supports a pathoge nic role. In addition, the variant is predicted to cause a frameshift, which al ters the protein's amino acid sequence beginning at codon 842 and leads to a pre mature stop codon 42 amino acids downstream. This alteration is then predicted t o lead to a truncated or absent protein (loss of function). Loss of function of the MYBPC3 gene is an established disease mechanism for HCM, which strongly supp orts a pathogenic role of the Tyr842fs variant. |
Agnes Ginges Centre for Molecular Cardiology, |
RCV000201921 | SCV000256647 | pathogenic | Hypertrophic cardiomyopathy 1 | 2015-05-30 | criteria provided, single submitter | research | The MYBPC3 Tyr842fs variant is absent from the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). We have identified this variant in 1 HCM proband (IVS 24mm). This MYBPC3 insertion variant (c.2525dupT) is predicted to interrupt the reading frame and lead to a premature stop codon, and a truncated or absent protein. Loss-of-function mutations in the MYBPC3 gene are an established mechanism of disease in HCM hence, we classify MYBPC3 Tyr842fs as "pathogenic". |
Invitae | RCV000035500 | SCV003439700 | pathogenic | Hypertrophic cardiomyopathy | 2022-09-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 42632). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 23396983, 27532257, 28615295). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr842Leufs*42) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). |