Table 1.

SQSTM1 and VCP rare genetic variants in patients with sIBM

Case ID	Gene and region	Variants (heterozygous)	MAF in 235 neuropathologic controls (%)	MAF in 1000 genomes (%)	MAF in ExAC (%)	MAF in sIBM cohort (%)	GERP++ score	PolyPhen prediction	Known in other diseases
Case 1 (sIBM)	SQSTM1 Exon 8	p.P392L (rs104893941)	0.213	0.46	0.089	0.275	4.43	Pathogenic	Familial PDB and ALS
Case 2 (sIBM)	SQSTM1 Exon 3	p.A117V (rs147810437)	0	0.18	0.152	0.275	−5.17	Benign	Early-onset AD
Case 3 (sIBM)	SQSTM1 Exon 4	p.G194R	0	—	0.0017	0.275	3.65	Possibly damaging	—
Case 4 (sIBM)	SQSTM1 Exon 5	p.K238E (rs11548633)	0.638	0.32	0.242	0.275	3.87	Possibly damaging	ALS
Case 5 (sIBM)	VCP Exon 2	p.I27V (rs140913250)	0	0.09	0.054	0.275	5.71	Benign	IBMPFD, ALS, and PD
Case 6 (sIBM) Case7 (sIBM)	VCP Exon 5	p.R159C	0	—	0.00082	0.549	4.62	Possibly damaging	IBMPFD, IBM with PD, and sporadic ALS

Key: A, alanine; AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; C, cysteine; E, glutamic acid; ExAC, Exome Aggregation Consortium; G, glycine; GERP, genomic evolutionary rate profiling; I, isoleucine; IBMPFD, inclusion body myopathy with Paget disease and frontotemporal dementia; K, lysine; L, leucine; MAF, minor allele frequency; P, proline; PD, Parkinson's disease; PDB, Paget disease of bone; R, arginine; sIBM, sporadic inclusion body myositis; SQSTM1, sequestosome 1; V, valine; VCP, valosin-containing protein.