TABLE 3.
Pathogenic and probably pathogenic variants identified in patients with extreme HDL-C
| Ref. Seq. | Nuc. Change | Amino Acid Change | rsID/Novel | HGMD | Functional Prediction | MAF | Phenotype | |
| Low HDL genes | ||||||||
| ABCA1 | NM_005502 | c.1196T>C | p.Val399Ala | rs9282543:G | DM | Tolerated | 0.002 | Low |
| ABCA1 | NM_005502 | c.1755C>A | p.Asp585Glu | Novel | — | Damaging | — | Low |
| ABCA1 | NM_005502 | c.1769G>T | p.Trp590Leu | Novel | DM | Damaging | — | Low |
| ABCA1 | NM_005502 | c.1913G>A | p.Arg638Gln | Novel | DM | Damaging | — | Low |
| ABCA1 | NM_005502 | c.2328G>C | p.Lys776Asn | rs138880920 | DP | Damaging | 0.003 | High |
| ABCA1 | NM_005502 | c.2540C>T | p.Pro847Leu | Novel | — | Damaging | — | Low |
| ABCA1 | NM_005502 | c.3338delT | p.Gln980Serfs*9 | Novel | — | — | — | Low |
| ABCA1 | NM_005502 | c.3121C>G | p.Leu1041Val | rs192935024 | — | Damaging | 0.001 | High |
| ABCA1 | NM_005502 | c.3541C>A | p.Ala1046Asp | rs141021096 | DM | Damaging | — | Low |
| ABCA1 | NM_005502 | c.3946C>T | p.Ser1181Phe | rs76881554 | DM | Damaging | 0.0006 | High |
| ABCA1 | NM_005502 | c.4449delC | p.Leu1484Cysfs*17 | Novel | — | — | — | Low |
| ABCA1 | NM_005502 | c.4939C>T | p.Thr1512M | Novel | DM | Damaging | — | Low |
| ABCA1 | NM_005502 | c.5039G>A | p.Arg1680Gln | rs150125857 | DM | Damaging | 0.0002 | Low |
| ABCA1 | NM_005502 | c.5550G>T | p.Tryp1699Cys | rs146934490 | DM | Damaging | — | Low |
| ABCA1 | NM_005502 | c.5449C>T | p.Arg1817* | Novel | — | Damaging | — | Low |
| ABCA1 | NM_005502 | c.5702_5703dupGA | p.Ile1902Glufs*12 | Novel | — | — | — | Low |
| ABCA1 | NM_005502 | c.7002C>T | p.Arg2200* | Novel | — | Damaging | — | Low |
| ABCA1 | NM_005502 | c.6730G>A | p.Val2244Ile | rs144588452 | DM | Tolerated | 0.0004 | Low |
| APOA1 | NM_000039 | c.138C>T | p.Arg34* | Novel | — | Damaging | — | Low |
| APOA1 | NM_000039 | c.382T>A | p.Lys131Met | rs4882 | — | Damaging | — | Low |
| APOA1 | NM_000039 | c.391_393del | p.Lys131del | Novel | — | — | — | Low |
| LCAT | NM_000229 | c.451C>T | p.Thr147Ile | rs121908050 | DM | Damaging | — | Low |
| LCAT | NM_000229 | c.487G>A | p.Arg159Gln | Novel | DM | Damaging | Low | |
| LCAT | NM_000229 | c.694T>A | p.Ser232Thr | rs4986970 | DM | Tolerated | 0.0084 | Both |
| LCAT | NM_000229 | c.1043C>A | p.Thr348Ile | Novel | — | Damaging | — | Low |
| LCAT | NM_000229 | c.1103G>T | p.Gly368Val | Novel | DM | Damaging | — | Low |
| NPC1 | NM_000271 | c.665A>G | p.Asn222Ser | rs55680026 | DM | Tolerated | 0.003 | Both |
| NPC1 | NM_000271 | c.3308G>T | p. Gly1012Cys | Novel | — | Damaging | Low | |
| NPC1 | NM_000271 | c.3689T>C | p.Leu1230Ser | Novel | — | Damaging | — | High |
| High HDL genes | ||||||||
| CETP | NM_000078 | c.118+1-118+4delGTAA | splice site | Novel | DM | — | — | High |
| CETP | NM_000078 | c.1376A>G | p.Asp459Gly | rs2303790 | DM | Damaging | 0.0062 | High |
| LIPG | NM_006033 | c.716T>C | p.Ile239Thr | Novel | DM | Damaging | — | High |
| LIPG | NM_006033 | c.1069G>T | p.Glu273* | Novel | — | Damaging | High | |
| LIPG | NM_006033 | c.1426C>T | p.Arg476Trp | rs117623631 | DM | Damaging | 0.003 | High |
| SCARB1 | NM_001082959 | c.715G>A | p.Gly239Arg | Novel | — | Damaging | — | Low |
MAF is based on 1000 Genomes CEU (Utah residents with ancestry from northern and western Europe) data. Functional prediction based on SIFT. DM, disease-causing mutation in HGMD; DP, disease-associated polymorphism in HGMD; Ref. Seq., reference sequence; Nuc., nulceotide; rsID, reference SNP identification. Phenotype refers to whether the variant was detected in a patient (or patients) with low HDL-C, high HDL-C, or in both groups of patients.