Table 2 Pathogenicity and population frequency analysis of IARS2 variants
From: Expanding the clinical phenotype of IARS2-related mitochondrial disease
IARS2 Alleles | c.2725C > T, p.Pro909Ser (Present study) | c.2726C > T, p.Pro909Leu | c.2620G > A, p.Gly874Arg | c.2282A > G, p.His761Arg (Present study) | c.680 T > C, p.Phe227Ser | c.2450G > A, p.Arg817His | c.2122G > A, p.Glu708Lys | c.1821G > A, p.Trp607* | c.607G > C p.Gly203Arg | c.2446C > T p.(Arg816*) | c.2575 T > C p.(Phe859Leu) |
|---|---|---|---|---|---|---|---|---|---|---|---|
Phenotypes | CAGSSS | CAGSSS | CAGSSS | Cataract,SD | CAGSSS,Leigh, and West syndrome | CAGSSS,Leigh, and West syndrome | Leigh syndrome | Leigh syndrome | Cataract | Cataract | Cataract |
FATHMM | Tolerated (2.93) | Tolerated (2.615) | Tolerated (2.77) | Tolerated (2.57) | Tolerated (0.76) | Tolerated (2.38) | Tolerated (0.96) | No entry | Tolerated (−0.77) | No entry | Tolerated (2.62) |
MutationAssessor | Low (1.175) | Medium (2.615) | Medium (2.1) | Medium (2.76) | High (4.34) | High (3.89) | Medium (2.955) | No entry | High (4.265) | No entry | Medium (2.63) |
MutationTaster | Disease causing (1) | Disease causing (1) | Disease causing (1) | Disease causing (1) | Disease causing (1) | Disease causing (1) | Disease causing (1) | No entry | Disease causing (1) | No entry | Disease causing (1) |
PolyPhen-2 | Benign (0.426) | Probably damaging (0.983) | Probably damaging (1.00) | Probably damaging (1.00) | Probably damaging (1.00) | Probably damaging (1.00) | Possibly damaging (0.935) | No entry | Probably damaging (1.00) | No entry | Probably damaging (1.00) |
SIFT | Tolerated (0.08) | Deleterious (0.03) | Tolerated (0.41) | Tolerated (0.1) | Deleterious (0) | Tolerated (0.06) | Tolerated (0.06) | No entry | Deleterious (0.01) | No entry | Tolerated (0.4) |
Ensembl | Not present | Not present | Not present | Not present | Not present | Allele count: 3; 0 homozygous | Allele count: 6; 1 homozygous | Allele count: 1; 0 homozygous | Not present | Allele count: 1; 0 homozygous | Allele count: 2; 0 homozygous |
EVS | Not present | Not present | Allele count: 1; 0 homozygous | Not present | Not present | Allele count: 3; 0 homozygous | Allele count: 11; 0 homozygous | Allele count: 1; 0 homozygous | Not present | Not present | Not present |
GME | Not present | Not present | Not present | Not present | Not present | Allele count: 4; 0 homozygous | Allele count: 3; 1 homozygous | Not present | Not present | Not present | Not present |
gnomAD | Not present | Not present | Allele count: 6; 0 homozygous | Not present | Not present | Allele count: 4; 0 homozygous | Allele count: 369; 6 homozygous | Allele count: 1; 0 homozygous | Not present | Allele count: 3; 0 homozygous | Allele count:39; 0 homozygous |
Iranome | Not present | Not present | Not present | Not present | Not present | Not present | Allele count: 1 | Not present | Not present | Not present | Not present |