Table 1.
PCSK9 rare variants identified and characteristics of carrier patients.
| Patient ID | Nucleotide substitution | Protein change | Variant ID, MAF* and reference | Total cholesterol (mmol/L) | LDL cholesterol (mmol/L) | HDL cholesterol (mmol/L) | Triglycerides (mmol/L) | Age (years) | Sex |
|---|---|---|---|---|---|---|---|---|---|
| FH-1 | c.103 G > T | p.(Asp35Tyr) | rs764603059; gnomAD: 0.00001; NF† ExAC, EVS, 1 kG16 | 8.7 | 5.8 | 1.9 | 2.2 | 21 | Female |
| FH-2 | c.991 C > G | p.(Pro331Ala) | NF† ExAC, gnomAD, EVS, 1 kG | 7.7 | 4.8 | 2.4 | 55 | Female | |
| FH-3 | c.1069 C > T | p.(Arg357Cys) | rs148562777; ExAC: 0.00015; gnomAD: 0.00015; EVS: 0.0002; NF† 1 kG | 4.6 ‡ | 2.9‡ | 1.3‡ | 0.8‡ | 9 | Male |
| FH-4 | c.1394 C > T | p.(Ser465Leu) | rs778849441; gnomAD: 0.00002; NF† ExAC, EVS, 1 kG17,18 | 11.6 | 8.4 | 1.5 | 3.7 | 65 | Female |
| FH-5 | c.1405 C > T | p.(Arg469Trp) | rs141502002; ExAC:0.0007 (0.007 in African; 0.0003 in others); gnomAD: 0.00087 (0.009 in African; 0.0005 in others); EVS: 0.0027 (only African/American); 1 kG: 0.0018 (only African)19–21 | 5.0 | 3.2 | 1.5 | 0.4 | 8 | Female |
| FH-6§ | c.1906A > C | p.(Ser636Arg) | NF† ExAC, gnomAD, EVS, 1 kG | 9.4 | 6.6 | 2.0 | 1.8 | 21 | Female |
| FH-7 | c.1928A > G | p.(His643Arg) | NF† ExAC, gnomAD, EVS, 1 kG | 7.4 | 5.4 | 1.4 | 1.2 | 30 | Male |
*Minor Allele Frequency according to exome/genome databases (ExAC: Exome Aggregation Consortium; gnomAD: Genome Aggregation Database; EVS: Exome Variant Server; 1 kG: 1000 Genomes).
†NF = Not found.
‡Biochemical values evaluated during a very restrictive diet.
§The patient also carries the LDLR variant p.(Leu446Val) that does not cause alteration of LDLR activity.