FH = familial hypercholesterolemia; NA = not applicable

Genes are listed in alphabetic order

See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Sturm et al [2018]

Sequence analysis of LDLR should include the regulatory region (200 bp upstream of the initiation codon).

To date, only ~30 LDLRAP1 pathogenic variants have been identified, and most have been biallelic loss-of-function variants [Fahed & Nemer 2011, Cuchel et al 2014, Hegele 2019, Petrulioniene et al 2019, D'Erasmo et al 2020, Kamar et al 2021, Nikasa et al 2021].

Whole-gene duplication was reported in two unrelated families with FH [Iacocca et al 2018].

FH disease-causing pathogenic variant(s) can be identified in ∼60%-80% of adult probands with a clinical diagnosis of FH. FH disease-causing pathogenic variant(s) can be identified in ∼60%-95% of pediatric probands in whom there is a strong clinical suspicion of FH [Sturm et al 2018]. Therefore, in ~40% of individuals with a clinical diagnosis of FH, a genetic cause cannot be identified.