Table 5 Fourteen novel putative pathogenic variants associated with familial hypercholesterolemia in the Qatar Genome Program study
From: Assessing the genetic burden of familial hypercholesterolemia in a large middle eastern biobank
Gene | HGV_DNA | HGV_P | QGP AC | QGP subclusters | DLCN criteria | Estimated clinical Penetrance | LDL-C (mmol/L) | Self-reported HC | ACMG classification |
|---|---|---|---|---|---|---|---|---|---|
ABCG8 | c.391Â C>T | p.Gln131* | 2 | QGP_WEP | . | . | . | . | LP (PVS1, PM2, PP3) |
APOB | c.8936G>A | p. Gly2979Asp | 1 | QGP_ADM | 1 Probable | 100% (1/1) | 8.7 | Yes | VUS (PM2, BP4) |
APOB | c.7106Â A>G | p. Lys2369Arg | 2 | QGP_WEP | 1 Probable | 50% (1/2) | 7.7 | Yes | VUS (PM2, BP4) |
APOB | c.4412T>G | p. Leu1471Trp | 5 | QGP_ADM (1), QGP_WEP (4) | 1 Possible | 20% (1/5) | 6 | Yes | VUS (PM2, BP4) |
APOB | c.9336G>T | p. Glu3112Asp | 3 | QGP_WEP | 1 Probable | 33% (1/3) | 9.2 | Yes | VUS (PM2) |
APOB | c.9547Â A>G | p. Arg3183Gly | 6 | QGP_GAR | 1 Possible | 16% (1/6) | 6.1 | Yes | VUS (PM2, BP4) |
APOB | c.1697T>C | p. Met566Thr | 11 | QGP_GAR (4), QGP_PAR (7) | 2 Possible | 18% (2/11) | 5.6, 6.6 | Yes, yes | VUS (PM2) |
APOB | c.4780Â C>A | p. Gln1594Lys | 10 | QGP_WEP | 1 Probable, 1 Possible | 20% (2/10) | 6.6, 6 | Yes, yes | VUS (PM2) |
LDLR | c.1414G>A | p. Asp472Asn | 8 | QGP_ADM (1), QGP_GAR (7) | 1 Possible | 14% (1/8) | 5.1 | Yes | LP (PM1, PM2, PP2, PP3, BP1) |
LDLRAP1 | C.200Â C>T | p. Ser67Leu | 39 | QGP_WEP | . | 0% (0/1) * | . | Yes | VUS (PM1, PM2, PP4) |
LIPA | C.149Â A>C | p.Glu50Ala | 1 | QGP_ADM | . | . | Â | Â | LP (PM1, PM2, PM5, PP3) |
PCSK9 | c.175G>C | #p. Gly59Arg | 1 | QGP_AFR | 1 Possible | 100% (1/1) | 6 | Yes | VUS (PM2, BP4) |
PCSK9 | c.203Â C>A | #p. Ala68Asp | 1 | QGP_AFR | 1 Possible | 100% (1/1) | 6 | Yes | VUS (PM2) |
PCSK9 | c.908G>A | p. Arg303His | 3 | QGP_ADM (2), QGP_WEP (1) | 1 Possible | 33% (1/3) | 6.5 | Yes | VUS (PM1, PM2) |