Table 2.
Genetic information of the novel pathogenic and likely pathogenic variants.
| ACMG | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Nucleotide change | Amino acid change | SIFT | PP2 | PROVEAN | MA | Condel | Same codon reference | Reference AA change | Strong | Moderate | Support | Classification |
| c.154G>A | p.Glu52Lys | 0.003 | 0.901 | −2.97 | 2.58 | 0.64 | No | — | — | PS4‐modarate, PM2 | PP1, 3, 4 | Likely pathogenic |
| c.313A>T | p.Thr105Ser | 0 | 1 | −3.68 | 3.53 | 0.57 |
Kijima et al. (
2005
)
Sitarz et al. ( 2012 ) Brozkova et al. ( 2013 ) |
Thr105Met Thr105Ala Thr105Arg |
— | PS4‐modarate, PM2, 5 | PP3, 4 | Likely pathogenic |
| c.326A>G | p.Lys109Arg | 0 | 1 | −2.66 | 4.065 | 0.78 | No | — | PS2 | PS4‐modarate, PM2 | PP3 | Pathogenic |
| c.382C>T | p.His128Tyr | 0 | 0.987 | −5.52 | 3.375 | 0.64 | Calvo et al. ( 2009 ) | His128Arg | — | PS4‐modarate, PM2, 5, 6 | PP3 | Likely pathogenic |
| c.389C>T | p.Thr130Ile | 0 | 0.975 | −5.42 | 3.94 | 0.68 | No | — | — | PS4‐modarate, PM1, 2 | PP3, 4 | Likely pathogenic |
| c.658G>A | p.Ala220Thr | 0 | 0.975 | −3.49 | 2.575 | 0.59 | No | — | — | PS4‐modarate, PM2, 6 | PP3 | Likely pathogenic |
| c.733A>C | p.Ser245Arg | 0.003 | 0.57 | −3.18 | 2.23 | 0.55 | No | — | — | PS4‐modarate, PM1, 2 | PP3, 4 | Likely pathogenic |
| c.1078C>G | p.Gln360Glu | 0.003 | 0.81 | −2.44 | 3.07 | 0.62 | No | — | — | PS4‐modarate, PM1, 2 | PP3, 4 | Likely pathogenic |
| c.1147_1149delGCT | p.Ala383del | — | — | −6.62 | — | — | Muglia et al. ( 2007 ) | Ala383Val | — | PS4‐modarate, PM1, 2 | PP4 | Likely pathogenic |
| c.1427G>C | p.Arg476Pro | 0.006 | 0.94 | −2.83 | 2.34 | 0.58 | No | — | — | PS4‐modarate, PM2 | PP1, 3, 4 | Likely pathogenic |
| c.1636T>G | p.Ser546Ala | 0 | 0.999 | −2.64 | 3.08 | 0.58 | No | — | — | PS4‐modarate, PM2, 6 | PP3 | Likely pathogenic |
| c.2075T>G | p.Leu692Arg | 0 | 1 | −4.9 | 2.375 | 0.62 | No | — | — | PS4‐modarate, PM2, 6 | PP3 | Likely pathogenic |
| c.2222T>C | p.Leu741Ser | 0 | 1 | −4.45 | 2.455 | 0.63 | No | — | — | PS4‐modarate, PM1, 2 | PP3, 4 | Likely pathogenic |
| c.2240T>G | p.Met747Arg | 0.53 | 0.001 | −0.72 | −0.05 | 0.48 | Calvo et al. ( 2009 ) | Met747Thr | — | PS4‐modarate, PM2, 5 | PP1, 4 | Likely pathogenic |
| c.2243_4insT | p.Thr749Hisfs*14 | — | — | — | — | — | No | — | — | PS4‐modarate, PM1, 2, 4 | PP4 | Likely pathogenic |
AA, amino acid; ACMG, American College of Medical Genetics and Genomics; MA, mutation assessor; PP2, PolyPhen2.
In silico analysis cut off: SIFT <0.05, PP2 >0.9, PROVEAN <−2.5, MA >1.9, and Condel >0.47.