Conclusion and results
The variant in PDLIM7 was a missense variant
(NM_005451.5(PDLIM7)c.716C>T p.(Thr239Met)) (AMCG
classification: variant of unknown significance - PM2 and PP3).
Literature search on PDLIM7 revealed that the gene was involved
in cardiac valve formation. The frequency of the variant was very rare
in the population database GnomAD v2.1.1 (0.0012%) and the variant was
absent in our in-house database. The variant involved a moderately
conserved nucleotide (PhyloP 3.68) and amino acid (considering 12
species) and the functional annotation algorithms Polyphen2 and SIFT
predicted a probably damaging or deleterious effect of the variant. By
testing other family members, co-segregation was shown, even though one
carrier (III.3) showed no phenotype at age of 29. However, incomplete
penetrance and variable age of onset is common in genetic cardiac
disorders.