ClinVar

Description

Variant summary: MYBPC3 c.3288delG (p.Glu1096AspfsX93) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 210992 control chromosomes. c.3288delG has been reported in the literature in multiple individuals affected with Hypertrophic Cardiomyopathy (examples- Lekanne_2006, Waldmuller_2011, Kapplinger_2014, Bos_2014, Walsh_2017, van Lint_2019). These data indicate that the variant is very likely to be associated with disease, however at least one publication reports the variant in an unaffected individual, suggesting imcomplete penetrance (Lekanne_2006). One publication reports that mRNA with the variant could not be detected in the peripheral blood of a patient with this mutation, indicating nonsense-mediated decay (Lekanne_2006). Six other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as pathogenic (n=5) and uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.