Table 1.

Candidate variants in 4 probands with dystonia

Disease model	Gene	pLI score (ExAC)	missense Z score (ExAC)	Known disease annotation (OMIM)	Variation nucleotidea	Variation amino acida	Variant type	Frequency ExAC; dbSNP142	Frequency in-house exomesb	CADD score	Carrier #	Sex	Age at onset, y	Dystonia type	Family history	Comment on putative disease relevance
Autosomal-dominant	NOL4	1.0	2.7	no	c.457C>T	p.Arg153X	stop-gain	not found; not found	not found	37	case_224	F	4	segmental isolated dystonia (cervical dystonia, upper limb dystonic tremor)	positive	loss-of-function variant in gene with pLI≥0.9
Autosomal-dominant	SLC35F1	0.39	2.01	no	c.152G>T	p.Arg51Met	missense	not found; not found	not found	30	case_112	M	26	focal isolated dystonia (tremulous cervical dystonia)	negative	mutational recurrence at codon-51 in gene with missense Z score ≥2.0
Autosomal-dominant	SLC35F1	0.39	2.01	no	c.152G>C	p.Arg51Thr	missense	not found; not found	not found	24	case_122	M	33	focal isolated dystonia (tremulous cervical dystonia	negative	mutational recurrence at codon-51 in gene with missense Z score ≥2.0
Autosomal-dominant	SLC40A1	0.98	1.77	MIM606069	c.469G>C	p.Asp157His	missense	not found; not found	not found	31	case_088	F	44	focal isolated dystonia (cervical dystonia)	positive	mutational recurrence at codon-157, a site previously associated with hemochromatosis 4

Sex: M = male, F = female. ExAC = exome aggregation consortium, Cambridge, MA (http://exac.broadinstitute.org). pLI = probability of being loss-of-function intolerant. OMIM = Online Mendelian Inheritance in Man (https://omim.org/). CADD = Combined Annotation Dependent Depletion.

^anumbering according to NCBI accessions NM_003787.4 and NP_003778.2 for NOL4, NM_001029858.3 and NP_001025029.2 for SLC35F1, NM_014585.5 and NP_055400.1 for SLC40A1, and NM_006931.2 and NP_008862.1 for SLC2A3.

^bconsisting of roughly 10,000 non-dystonia control exomes.