Table 1.
Known pathogenic variants from ClinVar or literature review that are represented in gnomAD sequence database.
| Gene | Consequence | Source1 | Clinical Sign.2 | Predicted effect on protein function | Carriers | Allele Freq. | |||
|---|---|---|---|---|---|---|---|---|---|
| Lit. | Lab | PolyPhen2 | SIFT | LoF | |||||
| PDSS1 | p.Asp308Glu | 1 | 0 | P | prob. damaging | deleterious | 1 | 4.07E-06 | |
| PDSS2 | p.His92Pro | 0 | 1 | LP | prob. damaging | deleterious | 11 | 3.97E-05 | |
| p.Gln322* | 1 | 0 | P | N/A | N/A | high-conf. | 1 | 4.07E-06 | |
| p.Ser382Leu | 1 | 0 | P | prob. damaging | deleterious | 7 | 2.84E-05 | ||
| COQ2 | p.Ser146Asn | 1 | 0 | P | prob. damaging | deleterious | 4 | 1.67E-05 | |
| p.Arg197His | 1 | 0 | P | prob. damaging | deleterious | 2 | 8.14E-06 | ||
| p.Asn228Ser | 1 | 0 | P | benign | deleterious | 32 | 1.16E-04 | ||
| p.Leu234Argfs*14 | 1& | 0 | N/A | N/A | N/A | high-conf. | 1 | 4.19E-06 | |
| p.Tyr297Cys | 1 | 0 | P | prob. damaging | deleterious | 1 | 4.11E-06 | ||
| p.Thr317Met | 0 | 1 | P | prob. damaging | deleterious | 5 | 2.72E-05 | ||
| p.Gly390Ala | 1& | 0 | N/A | prob. damaging | deleterious | 6 | 2.45E-05 | ||
| p.Asn401Ilefs*15 | 1 | 0 | P | N/A | N/A | high-conf. | 3 | 1.23E-05 | |
| COQ4 | p.Pro64Ser | 1 | 0 | P | prob. damaging | deleterious | 2 | 9.07E-06 | |
| p.Asp68His | 1 | 0 | P | prob. damaging | deleterious | 10 | 4.22E-05 | ||
| p.Pro119Leu | 0 | 1 | LP | prob. damaging | deleterious | 3 | 1.22E-05 | ||
| p.Arg145Gly | 1 | 0 | P | prob. damaging | tolerated | 1 | 4.75E-06 | ||
| p.Arg240Cys | 2 | 1 | P | prob. damaging | deleterious | 47 | 1.72E-04 | ||
| COQ6 | p.Pro261Leu | 1& | 0 | N/A | prob. damaging | deleterious | 19 | 6.86E-05 | |
| p.Asn380Ser | 0 | 1 | LP | prob. damaging | deleterious | 6 | 2.16E-05 | ||
| COQ8A | c.589–3 C > G | 1& | 0 | N/A | N/A | N/A | conf.3 | 1 | 3.23E-05 |
| p.Arg213Trp | 1 | 0 | P | prob. damaging | damaging | 2 | 6.46E-05 | ||
| p.Arg213Glnfs*71 | 0 | 1 | P | N/A | N/A | high-conf. | 1 | 4.07E-06 | |
| p.Arg271Cys | 2 | 1 | LP;US | prob. damaging | deleterious | 29 | 1.08E-04 | ||
| p.Leu277Pro | 0 | 1 | LP | pos. damaging | deleterious | 1 | 4.49E-06 | ||
| p.Arg299Trp | 1& | 0 | N/A | prob. damaging | deleterious | 8 | 2.89E-05 | ||
| p.Ala304Thr | 1& | 0 | N/A | prob. damaging | deleterious | 4 | 1.63E-05 | ||
| p.Ala304Val | 0 | 1 | LP | prob. damaging | deleterious | 11 | 3.97E-05 | ||
| p.Arg348Ter | 0 | 1 | P | N/A | N/A | high-conf. | 10 | 4.04E-05 | |
| p.Leu379* | 1 | 0 | N/A | N/A | N/A | high-conf. | 1 | 4.06E-06 | |
| p.Arg410* | 0 | 1 | N/A | N/A | N/A | high-conf. | 5 | 1.82E-05 | |
| p.Thr445Argfs*52 | 0 | 1 | P | N/A | N/A | high-conf. | 1 | 4.07E-06 | |
| p.Thr511Met | 0 | 1 | LP | pos. damaging | deleterious | 13 | 4.69E-05 | ||
| p.Gly549Ser | 1 | 0 | P | prob. damaging | deleterious | 35 | 1.27E-04 | ||
| p.Glu551Lys | 1 | 0 | P | prob. damaging | deleterious | 5 | 1.81E-05 | ||
| p.Met555Ile | 1 | 0 | LP | pos. damaging | deleterious | 41 | 1.49E-04 | ||
| p.Glu568* | 0 | 1 | P | N/A | N/A | high-conf. | 1 | 4.07E-06 | |
| p.Ser582Glufs*148 | 0 | 1 | P | N/A | N/A | high-conf. | 4 | 1.63E-05 | |
| p.Thr584del | 1 | 1 | P | N/A | N/A | N/A4 | 30 | 1.22E-04 | |
| p.Pro602Arg | 1& | 0 | N/A | prob. damaging | deleterious | 9 | 3.25E-05 | ||
| p.Pro602Gln | 0 | 1 | P | prob. damaging | deleterious | 10 | 4.06E-05 | ||
| p.Ser616Leufs*114 | 0 | 1 | P | N/A | N/A | high-conf. | 16 | 5.77E-05 | |
| COQ8B | p.Phe215Leufs*14 | 1 | 0 | N/A | N/A | N/A | high-conf. | 10 | 3.67E-05 |
| p.Asp286Gly | 1 | 0 | P | pos. damaging | deleterious | 4 | 1.45E-05 | ||
| p.Arg320Trp | 1 | 0 | P | prob. damaging | deleterious | 5 | 2.03E-05 | ||
| p.His400Glnfs*11 | 1 | 0 | P | N/A | N/A | high-conf. | 1 | 4.06E-06 | |
| p.Glu447Glyfs*10 | 1& | 0 | N/A | N/A | N/A | high-conf. | 6 | 2.48E-05 | |
| p.Glu483* | 1 | 0 | P | N/A | N/A | high-conf. | 11 | 4.83E-05 | |
| COQ9 | c.521 + 1delG | 1 | 1 | P | N/A | N/A | high-conf. | 1 | 4.08E-06 |
| p.Arg244* | 1 | 0 | P | N/A | N/A | high-conf. | 3 | 1.22E-05 | |
| Sum: | 441 | 1.76E-03 | |||||||
See Table S2 for more information on all known pathogenic variants.
1Number of reports in the peer-reviewed literature (&: sources not included in ClinVar) or directly submitted by testing labs.
2Clinical significance, as stated in ClinVar record: Pathogenic, Likely Pathogenic, Uncertain Significance.
3Acceptor splice site mutation c.589–3 C > G demonstrated by in vitro model to result in non-functional product p.Leu197Valfs*20.
4In-frame deletion; mutant ADCK3 failed to rescue growth in ADCK3-null yeast.