Table 2.

Missense variants of APOE listed at the human genomic variant database ClinVar

Variation ID	Variant type	dbSNP ID	Locationa	Amino acid changeb	CADD (GRCh38-v1.6)	Anotation of the variant	Related disease
17849	SNV	rs121918392	c.61 G > A	p.Glu21Lys	20.20	Pathogenic	Hyperlipoproteinemia, type III; and atherosclerosis (APOE ε5)
440842	SNV	rs201672011	c.91 G > A	p.Glu31Lys	15.87	Pathogenic	NA
441264	Haplotype	rs201672011 - rs769455	c.[91 G > A;487 C > T]	p.Glu31Lys - p.Arg163Cys	15.87–28.40	Pathogenic	Familial hyperlipoproteinemia, type III
17880	SNV	rs121918399	c.127 C > T	p.Arg43Cys	23.30	Likely pathogenic	Lipoprotein glomerulopathy
242765	SNV	rs769452	c.137 T > C	p.Leu46Pro	0.72	Conflicting interpretations: benign, likely benign, uncertain significance	Alzheimer’s disease
441268	Haplotype	rs769452 - rs429358	c.[137 T > C;388 T > C]	p.Leu46Pro - p.Cys130Arg	0.72–16.65	Pathogenic/likely pathogenic	Familial hypercholesterolemia
17871	SNV	rs28931576	c.178 A > G	p.Thr60Ala	15.46	Pathogenic	NA
441269	Haplotype	rs11083750 - rs429358	c.[305 C > G;388 T > C]	p.Pro102Arg - p.Cys130Arg	23.20–16.65	Association	NA
441270	Haplotype	rs28931577 - rs267606662	c.[349 G > A;508 G > C]	p.Ala117Thr - p.Ala170Pro	27.00–17.41	Pathogenic	NA
88639	SNV	rs587778876	c.364 C > A	p.Leu122Met	24.00	Not provided	Major depressive disorder
17864	SNV	rs429358	c.388 T > C	p.Cys130Arg	16.65	Conflicting interpretations: pathogenic, likely pathogenic, risk factor, drug response, uncertain significance	Alzheimer’s disease; lipoprotein glomerulopathy; and warfarin response
694585	Haplotype	rs429358 - rs121918393	c.[388 = ;460 C > A526 = ]	p.Cys130Arg - p.Arg154Ser	16.65–25.30	Protective	Alzheimer’s disease (APOEε3_Christchurch)
440870	Haplotype	rs429358 - rs387906567	c.[388 T > C;478 C > T]	p.Cys130Arg - p.Arg160Cys	16.65–28.60	Pathogenic	Familial hyperlipoproteinemia, type III
441267	Haplotype	rs429358 - rs267606661	c.[388 T > C;805 C > G]	p.Cys130Arg - p.Arg269Gly	16.65–23.30	Pathogenic	Familial hyperlipoproteinemia, type III
917851	SNV	rs1969863273	c.422 A > G	p.Gln141Arg	19.85	Uncertain significance	Familial hypercholesterolemia; familial hyperlipoproteinemia, type III; and hyperlipoproteinemia
478904	SNV	rs267606664	c.434 G > A	p.Gly145Asp	24.50	Uncertain significance	Hypercholesterolemia
441262	Haplotype	rs267606664 - rs7412	c.[434 G > A;526 C > T]	p.Gly145Asp - p.Arg176Cys	24.50–24.60	Pathogenic	Apolipoproteinemia E1
88640	SNV	rs587778877	c.451 C > A	p.Leu151Met	20.70	Not provided	Major depressive disorder
17874	SNV	rs28931578	c.455 G > A	p.Arg152Gln	24.90	Pathogenic	NA
17850	SNV	rs121918393	c.460 C > A	p.Arg154Ser	25.30	Pathogenic	Familial hyperlipoproteinemia, type III
375636	SNV	rs200703101	c.461 G > T	p.Arg154Leu	27.80	Likely pathogenic	Abnormal circulating lipid concentration
17851	SNV	rs769455	c.487 C > T	p.Arg163Cys	28.40	Benign	Familial hyperlipoproteinemia, type III
17865	SNV	rs121918397	c.488 G > A	p.Arg163His	22.70	Pathogenic	Familial hyperlipoproteinemia, type III
17879	SNV	rs121918397	c.488 G > C	p.Arg163Pro	25.60	Pathogenic	Lipoprotein glomerulopathy
17858	SNV	rs121918394	c.490 A > C	p.Lys164Gln	25.50	Pathogenic	Hyperlipoproteinemia, type III
17857	SNV	rs121918394	c.490 A > G	p.Lys164Glu	26.10	Pathogenic	Familial hyperlipoproteinemia, type III
1077013	SNV	NA	c.494 G > C	p.Arg165Pro	27.50	Likely pathogenic	Lipoprotein glomerulopathy
126456	3 bp microsatellite	rs515726148	c.497TCC[1]	p.Leu167del	–	Pathogenic	Sea-blue histiocyte syndrome
17848	SNV	rs7412	c.526 C > T	p.Arg176Cys	24.60	Drug response	Hypercholesterolemia; familial hyperlipoproteinemia, type III; warfarin response; atorvastatin response efficacy
441265	Haplotype	rs7412 - rs267606663	c.[526 C > T;725 G > A]	p.Arg176Cys - p.Arg242Gln	24.60–8.57	Pathogenic	Familial hyperlipoproteinemia, type III
441266	Haplotype	rs7412 - rs199768005	c.[526 C > T;761 T > A]	p.Arg176Cys - p.Val254Glu	24.60–25.20	Pathogenic	Familial hyperlipoproteinemia, type III
17862	SNV	rs121918396	c.683 G > A	p.Trp228Ter	35.00	Pathogenic	Hyperlipoproteinemia, type III (APOE ε3_Washington); and familial hyperlipoproteinemia, type III
1315806	SNV	rs567353589	c.688 G > A	p.Glu230Lys	11.14	Uncertain significance	Lipoprotein glomerulopathy
17859	SNV	rs121918395	c.736 C > T	p.Arg246Cys	24.20	Pathogenic	NA
441263	Haplotype	rs140808909 - rs190853081	c.[784 G > A;787 G > A]	p.Glu262Lys - p.Glu263Lys	23.20–24.80	Pathogenic	Hyperlipoproteinemia, type III; and atherosclerosis (APOE ε7)
17875	SNV	rs121918398	c.875 G > A	p.Arg292His	25.20	Pathogenic	NA
17876	SNV	rs28931579	c.940 A > C	p.Ser314Arg	13.28	Pathogenic	NA

SNV rs429358 and rs7412, which determine the three common APOE alleles (ε2, ε3, and ε4) are shown in bold. Genomic variants detected only in East Asians are underlined: database searched, gnomAD v2.1.1 and v3.1.2

[Web site] CADD https://cadd.gs.washington.edu; ClinVar https://www.ncbi.nlm.nih.gov/clinvar; gnomAD https://gnomad.broadinstitute.org.

CADD combined annotation dependent depletion, NA not assigned, SNV single nucleotide variant

^aPosition on the APOE-encoding sequence, 1–954 bp (ATG [Met] - TGA [Ter]: 317 aa).

^bPosition on the immature APOE protein consisting of 317 amino acids, including the N-terminal signal peptide region with 18 amino acids (position, 1–18)