Table 1:
COQ8A variants identified in this study
| Var. ID | Family ID | cDNA change | Protein change | Pred. effect | MAF gnomAD | CADD Score | SIFT | Poly Phen2 | fathmm MKL | HGMD/publ. |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 44 | c.11T>A | I4K | mis | 0.0001 | 22.70 | 0 | 0.02 | 0.94 | yes |
| 2 | 8 | c.124_125del | A42PfsTer21 | fs | - | - | - | - | no | |
| 3 | 8 | c.148C>T | Q50Ter | stop | - | 37.00 | - | - | 0.98 | yes |
| 4* | 48 | c.238C>T | H80Y | mis | 0.0064 | 15.81 | 0.03 | 0.04 | 0.87 | yes |
| 5 | 12,37 | c.248dup | H85AfsTer42 | fs | - | - | - | - | - | no |
| 6 | 1 | c.447del | R150EfsTer59 | fs | - | - | - | - | - | no |
| 7 | 16,35 | c.500_521delinsTTG | Q167LfsTer36 | fs | - | - | - | - | - | yes |
| 8 | 19,21,32 | c.589–3C>G | - | can | 0.0001 | 13.75 | - | - | 0.40 | yes |
| 9 | 36 | c.620C>T | P207L | mis | - | 26.90 | 0 | 1.00 | 0.97 | no |
| 10 | 33 | c.637C>T | R213W | mis | 0.0001 | 32.00 | 0 | 1.00 | 0.83 | yes |
| 11 | 43 | c.637C>G | R213G | mis | - | 27.50 | 0 | 1.00 | 0.86 | no |
| 12 | 38 | c.798_823dup | L275RfsTer16 | fs | - | - | - | - | - | no |
| 13 | 39 | c.802T>C | C268R | mis | - | 25.50 | 0 | 0.47 | 0.96 | no |
| 14 | 5,14,18,31 | c.811C>T | R271C | mis | 0.0001 | 27.20 | 0 | 1.00 | 0.93 | yes |
| 15 | 34 | c.815G>A | G272D | mis | - | 26.00 | 0 | 1.00 | 0.98 | yes |
| 16 | 33 | c.815G>T | G272V | mis | - | 25.90 | 0 | 1.00 | 0.99 | yes |
| 17 | 6,17,29 | c.895C>T | R299W | mis | 0.0001 | 32.00 | 0 | 0.97 | 0.91 | yes |
| 18 | 2,21,22,24,41 | c.901C>T | R301W | mis | 0.0001 | 23.20 | 0 | 0.99 | 0.47 | yes |
| 19 | 14 | c.910G>A | A304T | mis | 0.0001 | 25.10 | 0 | 0.97 | 0.97 | yes |
| 20 | 4,7 | c.911C>T | A304V | mis | 0.0001 | 25.20 | 0 | 0.99 | 0.96 | yes |
| 21* | 49 | c.976G>A | D326N | mis | 0.0001 | 23.40 | 0.11 | 0.10 | 0.92 | no |
| 22** | 51 | c.993C>T | F331= | crypt | 0.0159 | 8.59 | - | - | 0.09 | yes |
| 23 | 10 | c.1009G>A | A337T | mis | 0.0001 | 27.00 | 0 | 1.00 | 0.97 | no |
| 24 | 1,13 | c.1012G>A | A338T | mis | 0.0001 | 25.30 | 0 | 1.00 | 0.97 | no |
| 25 | 11 | c.1013C>T | A338V | mis | 0.0001 | 25.00 | 0 | 1.00 | 0.96 | no |
| 26 | 9 | c.1015G>A | A339T | mis | 0.0001 | 25.30 | 0 | 1.00 | 0.97 | yes |
| 27 | 42 | c.1024G>T | G342W | mis | - | 26.70 | 0 | 1.00 | 0.97 | no |
| 28 | 16,20,23 | c.1042C>T | R348Ter | stop | 0.0001 | 41.00 | - | - | 0.84 | yes |
| 29 | 9,30 | c.1081–1_1082dup | Q360_Y361insTer | can | - | - | - | - | - | yes |
| 30 | 38 | c.1205T>C | L402P | mis | 0.0001 | 29.60 | 0.01 | 1.00 | 0.97 | no |
| 31 | 29,50 | c.1228C>T | R410Ter | stop | 0.0001 | 40.00 | - | - | 0.91 | yes |
| 32 | 22 | c.1332_1336dup | E446AfsTer33 | fs | - | - | - | - | no | |
| 33 | 48 | c.1334_1335del | T445RfsTer52 | fs | - | 34.00 | - | - | - | yes |
| 34 | 6,45,46 | c.1358del | L453RfsTer24 | fs | - | 34.00 | - | - | - | yes |
| 35 | 2 | c.1399-3_1408del | - | can | - | - | - | - | - | no |
| 36 | 15 | c.1440delinsTT | E481Ter | fs | - | - | - | - | - | no |
| 37 | 5,18 | c.1460C>G | T487R | mis | - | 28.70 | 0 | 1.00 | 0.98 | yes |
| 38 | 28 | c.1523T>C | F508S | mis | - | 32.00 | 0 | 1.00 | 0.99 | yes |
| 39 | 3 | c.1532C>T | T511M | mis | 0.0001 | 24.50 | 0 | 0.94 | 0.97 | yes |
| 40 | 44 | c.1534C>T | R512W | mis | 0.0001 | 23.50 | 0 | 1.00 | 0.39 | no |
| 41 | 51 | c.1645G>A | G549S | mis | 0.0001 | 26.40 | 0.01 | 0.99 | 0.98 | yes |
| 42 | 17 | c.1651G>A | E551K | mis | 0.0001 | 32.00 | 0 | 1.00 | 0.98 | yes |
| 43 | 26,40,41 | c.1665G>A | M555I | mis | 0.0004 | 28.90 | 0 | 0.93 | 0.98 | yes |
| 44 | 25,45,46 | c.1702G>T | E568Ter | stop | 0.0001 | 54.00 | - | - | 0.98 | yes |
| 45 | 3,13 | c.1750_1752del | T584del | del | - | 22.70 | - | - | - | yes |
| 46 | 34 | c.1813dup | E605GfsTer125 | fs | - | - | - | - | - | yes |
| 47* | 50 | c.1821C>T | Y607= | crypt | 0.0001 | 22.60 | - | - | 0.93 | no |
| 48 | 19,27 | c.1844G>A | G615D | mis | - | 32.00 | 0 | 1.00 | 0.98 | yes |
Genomic positions according to genome build GRCh37/hg19. DNA changes based on ENST00000366777.3. Protein changes according to ensemble protein ID ENSP00000355739.3. Predicted effects: can = canonical splice, crypt = cryptic splice, del = deletion, fs = frameshift, mis = missense. MAF = minor allele frequency. CADD score = scaled Combined Annotation Dependent Depletion score; SIFT = Sorting Intolerant From Tolerant score; PolyPhen-2 = Polymorphism Phenotyping v2; fathmm-MKL = Functional Analysis through Hidden Markov Models; HGMD = Human Gene Mutation Database.
*
variant of unknown significance.
**
likely not pathogenic.