I'm doing a family study looking for novel cancer-associated variants in germ-line samples; the goal is to find candidate biomarkers which might be used for early detection. At an earlier step our analysis, we eliminated a family that showed a heterozygous mutation known to be associated with our cancer under the premise that this known mutation better explained the presence of the disease than any novel variant we may have found.
I've now found another mutation, strongly associated with out cancer, which we does not appear to be heterozygous. 2 out of 3 family members share this mutation with a within-family allele frequency of 0.5.
Trying to decide whether this means I need to discard this family from further consideration, adjust my thinking, or not worry about it. My current thinking is that it'd be safest to eliminate the family from consideration because the mutation pathogenic and found in the germline but I can't wrap my head around how the lack of a heterozygous pattern affects things. Does it absolutely mean the variant was not inherited? Can anyone help me get my thoughts straight?