Diverse phenotype with
Different mutations in the same gene
Different mutations may have different downstream effects
VCP mutations are found in ALS, FTD and inclusion body myopathy.
Nalbandian et al., 2011 
Different variants confer different levels of pathogenicity
SNCA point mutations are highly penetrant for PD while penetrance for dosage mutation is linked to copy number; common variants increase PD risk only slightly.
Singleton et al., 2016 
Same mutation in the same gene
Presence of modifier gene
TMEM106b minor allele is protective of FTD but not ALS in patients with C9orf72 repeat expansion.
van Blitterswijk et al., 2014 
FALS patients with SOD1 mutation and additional rare variants in ALS genes have reduced survival.
Pang et al., 2017 
Different effects in different cell lines
TGM6 mutation found in families with SCA and a family with leukemia.
Pan et al., 2014