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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

GeneTranscriptVariantNumber of DLB patientsGnomAD MAF (all populations)GnomAD NFE AC (Total NFE AN)Previously reportedAdditional informationRef
APPENST00000346798c.2020G > A
p.Glu674Lys
10Not presentIn AD: adjacent amino acid (p.A673T) protective, or (p.A673V) causes EOAD when homozygousVariant newly identified here. Adjacent amino acid plays a role in disease[22, 32]
CHCHD2ENST00000395422c.10G > A
p.Gly4Arg
10.000028404 (128432)1 LBD patient[54]
DCTN1ENST00000361874c.2339 T > C p.Ile780Thr20.000038895 (129150)1 patient with FALS, controlLow frequency in gnomAD, but also found in a control[35]
GRNENST00000053867c.827C > T p.Ala276Val10.0000070751 (129048)1 patient with an initial diagnosis of FTD which was changed to depressionVariant found in a patient included in a neurodegenerative disease cohort, but diagnosis was changed from FTD[76]
MAPTENST00000344290c.256G > A
p.Gly86Ser
10.000029014 (126300)1 patient with clinical FTDSegregation not proven[65]
NOTCH3ENST00000263388c.1732C > T, p.Arg578Cys10.000039892 (113234)Found in several CADASIL, but also seen in 1 controlHomozygous variant carrier had a mild phenotype[14, 33, 43, 68]
c.1733G > A p.Arg578His10.0000079800 (113200)p.Arg578Cys (different amino acid change) seen in CADASILDifferent amino acid change than previously reported, not cysteine changing[14]
c.1820G > A
p.Arg607His
10.0000040001 (112826)1 CADASIL, and a different amino acid change, p.Arg607Cys seen in several CADASIL patientsFiltered site in gnomAD, may be false positive. Not cysteine changing[1, 46, 67]
SQSTM1ENST00000389805c.1210A > G
p.Met404Val
10.000015913 (113732)Several families with Paget’s disease of boneVariant shown to cause Paget’s disease of bone (not FTD-ALS)[23, 30]
TBK1ENST00000331710c.1150C > T
p.Arg384Trp
10.000021284 (128892)p.Arg384Thr (different amino acid change) reported in 1 ALSDifferent 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
10.000085143 (128842)p.Arg384Thr (different amino acid change) reported in 1 ALSDifferent amino acid change than previously reported. Variation in the same amino acid in 2 different DLB cases in this study[12]
TIA1ENST00000433529c.1085C > T
p.Pro362Leu
10.000021212 (129146)2 s degree relatives with FTD/ALSUnreplicated 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