G4298A

# **General Information**

| **Position** | **4298** | **Variant** | **m.4298G\>A** | **Locus** | **MT\-TI** | **RNA** | **tRNA Ile** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | Pathogenic | **Pathogenicity** | Cfrm \[VUS\*] |

"Pathogenicity" status is derived from published literature or predictions from bioinformatics tools. Researchers and clinicians are cautioned that additional data and/or analysis may still be necessary to confirm the pathological significance of these variants. For more information, please see [Mitofam Info](https://mitofam.com/doc/385/).

# **Pedigree Information**

The **m.4298G\>A** variant in MT\-TI has been reported in 3 pedigrees. To date, 6 carriers have been reported. Reported mutation loads ranged from 0% to 56%, with a median of 4% overall; affected carriers showed mutation loads from 0% to 56%, with a median of 6\.5%; unaffected carriers showed mutation loads from 1%, with a median of 1%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (48\.7%) than in blood (1%). In one affected carrier, the mutation was undetectable in blood (0%) but exceeded 20% in muscle (56%). The main clinical manifestations among affected carriers included multiple sclerosis, CPEO, facial pain, rhabdomyolysis, chronic progressive external ophthalmoplegia, myalgias, myoglobinuria, nystagmus, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 4298 | m.4298G\>A |[ G4298A\-F1 ](https://mitofam.com/doc/632/)| Italy | Rhabdomyolysis, myoglobinuria, myalgias, upper limb girdle weakness, unstable gait | 1 | 0 | 2004 | [16120360](https://pubmed.ncbi.nlm.nih.gov/16120360/) |  |
| 2 | 4298 | m.4298G\>A |[ G4298A\-F2](https://mitofam.com/doc/633/) | UK | Chronic progressive external ophthalmoplegia, multiple sclerosis | 2 | 0 | 1998 | [9473477](https://pubmed.ncbi.nlm.nih.gov/9473477/) |  |
| 3 | 4298 | m.4298G\>A | G4298A\-F3 | UK | CPEO, Multiple Sclerosis | NA | NA | 2000 | [10611123](https://pubmed.ncbi.nlm.nih.gov/10611123/) |  |

# **Carrier Information**

| **No.** | **Position** | **Variant** | **Family ID** | **Carrier ID** | **Type (Fam/De novo/Uninf)** | **Gender (F/M)** | **Proband (Y/N)** | **Affected (Y/N)** | **Die/Alive(D/A)** | **Age** | **Blood Mutant Level** | **Muscle Mutant level** | **Urine Mutant level** | **Other Mutant level** | **Clinical Features** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 4298 | m.4298G\>A | G4298A\-F1 | G4298A\-F1\-II1 | Fam | M | Y | Y | A | 38 | 1% | 48\.7% | / | / | Rhabdomyolysis, myoglobinuria, myalgias, upper limb girdle weakness, unstable gait |  |
| 2 | 4298 | m.4298G\>A | G4298A\-F1 | G4298A\-F1\-I2 | Uninf | F | N | N | A | ND | 1% | / | / | / | Healthy |  |
| 3 | 4298 | m.4298G\>A | G4298A\-F2 | G4298A\-F2\-I2 | Uninf | F | Y | Y | A | 49 | 0 | 56% | / | 4%(F),9%(BM) | Facial pain, trigeminal neuralgia, paresthesia, optic atrophy, nystagmus, ptosis, ophthalmoparesis, chronic progressive external ophthalmoplegia, multiple sclerosis |  |
| 4 | 4298 | m.4298G\>A | G4298A\-F2 | G4298A\-F2\-II1 | Fam | F | N | N | A | 20 | / | / | / | / | Healthy |  |
| 5 | 4298 | m.4298G\>A | G4298A\-F2 | G4298A\-F2\-II2 | Fam | F | N | N | A | 20 | / | / | / | / | Healthy |  |
| 6 | 4298 | m.4298G\>A | G4298A\-F3 | G4298A\-F3\-P1 | Uninf | F | Y | Y | A | 51 | / | / | / | / | CPEO, Multiple Sclerosis |  |

For abbreviations and other usage instructions, please see [Mitofam Info](https://mitofam.com/doc/385/).