Skip to main content

Table 1 Heterozygous variants of uncertain clinical significance that were found in the DLB case cohort. The variant in DCTN1 was found in two DLB cases. All other variants were seen in single DLB cases. Variants are included in Table 1 if they were previously reported, but not fully established as pathogenic, and if they were present five times or less in the European (non-Finnish) population in gnomAD

From: Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies

Gene Transcript Variant Number of DLB patients GnomAD MAF (all populations) GnomAD NFE AC (Total NFE AN) Previously reported Additional information Ref
APP ENST00000346798 c.2020G > A
p.Glu674Lys
1 0 Not present In AD: adjacent amino acid (p.A673T) protective, or (p.A673V) causes EOAD when homozygous Variant newly identified here. Adjacent amino acid plays a role in disease [22, 32]
CHCHD2 ENST00000395422 c.10G > A
p.Gly4Arg
1 0.00002840 4 (128432) 1 LBD patient [54]
DCTN1 ENST00000361874 c.2339 T > C p.Ile780Thr 2 0.00003889 5 (129150) 1 patient with FALS, control Low frequency in gnomAD, but also found in a control [35]
GRN ENST00000053867 c.827C > T p.Ala276Val 1 0.000007075 1 (129048) 1 patient with an initial diagnosis of FTD which was changed to depression Variant found in a patient included in a neurodegenerative disease cohort, but diagnosis was changed from FTD [76]
MAPT ENST00000344290 c.256G > A
p.Gly86Ser
1 0.00002901 4 (126300) 1 patient with clinical FTD Segregation not proven [65]
NOTCH3 ENST00000263388 c.1732C > T, p.Arg578Cys 1 0.00003989 2 (113234) Found in several CADASIL, but also seen in 1 control Homozygous variant carrier had a mild phenotype [14, 33, 43, 68]
c.1733G > A p.Arg578His 1 0.000007980 0 (113200) p.Arg578Cys (different amino acid change) seen in CADASIL Different amino acid change than previously reported, not cysteine changing [14]
c.1820G > A
p.Arg607His
1 0.000004000 1 (112826) 1 CADASIL, and a different amino acid change, p.Arg607Cys seen in several CADASIL patients Filtered site in gnomAD, may be false positive. Not cysteine changing [1, 46, 67]
SQSTM1 ENST00000389805 c.1210A > G
p.Met404Val
1 0.00001591 3 (113732) Several families with Paget’s disease of bone Variant shown to cause Paget’s disease of bone (not FTD-ALS) [23, 30]
TBK1 ENST00000331710 c.1150C > T
p.Arg384Trp
1 0.00002128 4 (128892) p.Arg384Thr (different amino acid change) reported in 1 ALS Different amino acid change than previously reported. Variation in the same amino acid in 2 different DLB cases in this study [12]
c.1151G > A
p.Arg384Gln
1 0.00008514 3 (128842) p.Arg384Thr (different amino acid change) reported in 1 ALS Different amino acid change than previously reported. Variation in the same amino acid in 2 different DLB cases in this study [12]
TIA1 ENST00000433529 c.1085C > T
p.Pro362Leu
1 0.00002121 2 (129146) 2 s degree relatives with FTD/ALS Unreplicated report suggests this variant causes ALS/FTD [45]
  1. Ref Reference, MAF Minor Allele Frequency, gnomAD NFE Non-Finnish European, AC Allele Count, AN Allele Number, FTD/ALS Frontotemporal Dementia / Amyotrophic Lateral Sclerosis, CADASIL Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, EOAD Early Onset Alzheimer’s disease, FALS Familial Amyotrophic Lateral Sclerosis, SALS Sporadic Amyotrophic Lateral Sclerosis, LBD Lewy Body Disease, AD Alzheimer’s disease, PD Parkinson’s disease