Table 2. Characteristics of novel mutations in POLG.

Variant	Conservation of the amino acid	Domain	Occurrence at structure/function important regions	Polarity change	Charge change	Grantham score	SIFT prediction	PolyPhen-2 prediction	Found in EVS or 1000 genome project databases	Found in 100 controlsa	Familial segregation
p.Met464Thr	Yes	Pol	Subunit interface	NP to P	No	81	Tolerated	Probably damaging	No	No	Yes
p.Lys768Glu	Yes	L	Globular intrinsic processivity subdomain	No	Basic to acid	56	Damaging	Probably damaging	No	No	Yes
p.Leu79Phe	Yes	N-terminal domain	Adjacent to DNA-binding domain	No	No	22	Damaging	Probably damaging	No	No	Yes
p.Ser1080Ile	Yes	Pol	Small subdomain (residues 1050–1095), partially blocks the DNA-binding channel	P to NP	No	142	Damaging	Possibly damaging	No	No	Yes
p.Gln975*	Stop	Pol	Loss of the half C-terminal part of the polymerase domain	NA	NA	NA	NA	NA	No	No	NA

Abbreviations: EVS, exome variant server; Pol, polymerase domain; NP, non-polar; P, polar; NA, not available; L, linker domain; Exo, exonuclease domain.

^aGeographically matched healthy controls.