Table 11.

Familial Hypercholesterolemia: Notable Pathogenic Variants by Gene

Gene 1Reference
Sequences		DNA Nucleotide Change
(Alias 2)		Predicted Protein Change
(Alias 2)		Comment [Reference]
APOB NM_000384​.3
NP_000375​.3 		c.10580G>A 3
(9775G>A)		p.Arg3527Gln
(Arg3500Gln)		Founder variant in Amish; common variant in persons of European ancestry [Shen et al 2010]
c.10579C>T
(9774C>T)		p.Arg3527Trp
(Arg3500Trp)		Common variant in Asian populations [Calandra et al 2011]
LDLR NM_000527​.5
NP_000518​.1 		c.655_657delGGCp.Gly219delFounder variant in Ashkenazi Jews; 1:67 Ashkenazi Jewish from Lithuania are heterozygous [Durst et al 2001].
c.564C>Gp.Tyr188TerCommon variant in Druze of Golan Heights [Landsberger et al 1992]
c.925_931delCCCATCAp.Pro309LysfsTer59Founder variants in Finnish population [Lahtinen et al 2015]
c.1784G>Ap.Arg595Gln
NG_009060​.1 g.39215_47749del8535--
>10-kb del 2
[incl exon 1]		--Founder variant in French Canadians [Hobbs et al 1987]
LDLRAP1 NM_015627​.3
NP_056442​.2 		c.431dupA
(c.432_433insA)		p.His144GlnfsTer27Founder variant in Sardinians [Fellin et al 2015]
c.65G>Ap.Trp22Ter
PCSK9 NM_174936​.4
NP_777596​.2 		c.381T>Ap.Ser127ArgPenetrance is ~90% in heterozygotes [Dullaart 2017].
c.1120G>Tp.Asp374TyrPenetrance is high, w/onset at young age in heterozygotes [Naoumova et al 2005].

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1.

Genes from Table 1 in alphabetic order

2.

Variant designation that does not conform to current naming conventions. In this case, numbering is based on mature peptide before cleavage of signal peptide and corresponding nucleotides.

3.

From: Familial Hypercholesterolemia

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