G4412A

# **General Information**

| **Position** | **4412** | **Variant** | **m.4412G\>A** | **Locus** | **MT\-TM** | **RNA** | **tRNA Met** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | 76\.50% | **Pathogenicity** | Reported |

"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.4412G\>A** variant in MT\-TM has been reported in 2 pedigrees. To date, 5 carriers have been reported. Reported mutation loads ranged from 0% to 90%, with a median of 0% overall; affected carriers showed mutation loads from 0% to 90%, with a median of 6%; unaffected carriers showed mutation loads from 0%, with a median of 0%. In one affected carrier, the mutation was undetectable in blood (0%) and other tissue (0%) but exceeded 20% in muscle (90%). The main clinical manifestations among affected carriers included generalised status epilepticus for more than 2 h and bilateral hearing impairment and cataract.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 4412 | m.4412G\>A | [G4412A\-F1](https://mitofam.com/doc/665/) | UK | Seizures with myopathy \& retinopathy;Seizures | 3 | 1 | 2019 | [31022467](https://pubmed.ncbi.nlm.nih.gov/31022467/) |  |
| 2 | 4412 | m.4412G\>A | G4412A\-F1 | UK | Seizures with myopathy \& retinopathy;Seizures | 3 | 1 | 2021 | [34089906](https://pubmed.ncbi.nlm.nih.gov/34089906/) |  |
| 3 | 4412 | m.4412G\>A | G4412A\-F2 | Japan | Myopathy | ND | ND | 2021 | [34089906](https://pubmed.ncbi.nlm.nih.gov/34089906/) |  |

# **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 | 4412 | m.4412G\>A | G4412A\-F1 | G4412A\-F1\-I2 | Uninf | F | N | N | A | ND | 0 | / | 0 | 0%(BM)\_x000D\_ | Healthy |  |
| 2 | 4412 | m.4412G\>A | G4412A\-F1 | G4412A\-F1\-II1 | De novo | F | Y | Y | A | 16 | 0 | 0\.9 | 0\.07 | 6%(BM)\_x000D\_ | Generalised status epilepticus for more than 2 h |  |
| 3 | 4412 | m.4412G\>A | G4412A\-F1 | G4412A\-F1\-II2 | Uninf | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 4 | 4412 | m.4412G\>A | G4412A\-F1 | G4412A\-F1\-II3 | Uninf | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 5 | 4412 | m.4412G\>A | G4412A\-F2 | G4412A\-F2\-P1 | Uninf | F | Y | Y | D | 57 | / | / | / | 10%(F)\_x000D\_ | bilateral hearing impairment and cataract |  |

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