TABLE 1.
Variants identified in patients with mitochondrial diseases and their pathogenicity prediction scores.
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | ||
|---|---|---|---|---|---|---|
| Gender | Female | Female | Male | Female | Female | |
| Gene | GFM2 | NDUFAF5 | FASTKD2 | FOXRED1 | FH | |
| RefSeq | NM_032380.5 | NM_024120.5 | NM_001136193.2 | NM_017547.4 | NM_000143.4 | |
| cDNA change | c.569G>A | c.827G>C | c.496_497del | c.1261G>A | c.1358T>C | |
| Protein change | p.Arg190Gln | p.Arg276Pro | p.Leu166GlufsTer2 | p.Val421Met | p.Leu453Pro | |
| Genotype | Homozygous | Homozygous | Homozygous | Homozygous | Homozygous | |
| dbSNP ID | rs761283105 | - | rs1304003703 | rs199542988 | - | |
| GnomAD exome frequency v2.1 | 1.6e-5 | - | 6.572e-6 a | 1.2e-5 | - | |
| ACMG classification | Uncertain significance | Uncertain significance | Likely pathogenic | Uncertain significance | Likely pathogenic | |
| Prediction tools/threshold score | SIFT/<0.05 | Damaging (0.001) | Damaging (0.001) | Deleterious b | Damaging (0.003) | Damaging (0) |
| PolyPhen-2 HDIV/>0.453 | Deleterious (1) | Deleterious (1) | NA c | Deleterious (0.987) | Deleterious (1) | |
| FATHMM/<0 | Tolerated (−0.54) | Deleterious (−2.06) | NAc | Deleterious (−2.26) | Deleterious (−6.34) | |
| MetaLR/>0.5 | Deleterious (0.66) | Deleterious (0.79) | NAc | Deleterious (0.7551) | Deleterious (0.98) | |
| MetaSVM/>0 | Deleterious (0.5661) | Deleterious (0.7425) | NAc | Deleterious (0.6457) | Deleterious (1.042) | |
| DANN/>0.8 | Deleterious (0.9996) | Deleterious (0.9969) | NAc | Deleterious (0.9989) | Deleterious (0.9993) | |
| VEST3/>0.75 | Deleterious (0.428) | Deleterious (0.945) | NAc | Deleterious (0.222) | Deleterious (0.987) | |
| CADD/>20 | Deleterious (35) | Deleterious (34) | NAc | Deleterious (27.9) | Deleterious (32) | |
| PROVEAN/<-2.5 | Deleterious (−3.48) | Deleterious (−6.7) | NAc | Neutral (−2.27) | Deleterious (−6.5) | |
| Mutation assessor/>1.9 | Medium (2.84) | Medium (2.895) | NAc | Medium (2.595) | Medium (2.255) | |
| UMD predictor/≥75 | Probably polymorphism (57) | Deleterious (99) | NAc | Probably polymorphism (63) | Deleterious (84) | |
| M-CAP/> 0.025 | Deleterious (0.0504) | Deleterious (0.1844) | NAc | Deleterious (0.2961) | Deleterious (0.8812) | |
| LRT/D, N, and U | Deleterious | Deleterious | NAc | Deleterious | Deleterious | |
| Mutation taster/A, D, N, and P | Deleterious | Deleterious | Deleterious | Deleterious | Deleterious | |
| Deleteriousness predictions | 11/14 | 14/14 | 2/2 | 11/14 | 14/14 | |
a
In gnomAD, genome.
b
SIFT, indel.
c
NA: not applicable for this frameshift variant.