G4403A

# **General Information**

| **Position** | **4403** | **Variant** | **m.4403G\>A** | **Locus** | **MT\-TM** | **RNA** | **tRNA Met** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | 84\.80% | **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.4403G\>A** variant in MT\-TM has been reported in 2 pedigrees. To date, 4 carriers have been reported. Reported mutation loads ranged from 0% to 77%, with a median of 0% overall; affected carriers showed mutation loads from 0% to 77%, with a median of 31\.5%; unaffected carriers showed mutation loads from 0%, with a median of 0%. In one affected carrier, the mutation was undetectable in blood (0%) and urine (0%) but exceeded 20% in muscle (63%). The main clinical manifestations among affected carriers included and mild steppage gait, diffuse muscle atrophy and weakness, exercise intolerance, progressive muscle weakness and atrophy had a muscle biopsy characterized by a combination of dystrophic features, short stature, and unusual dystrophic features on muscle biopsy.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 4403 | m.4403G\>A | G4403A\-F1 | Filipino | Mitochondrial Myopathy | ND | ND | 2014 | [24711008](https://pubmed.ncbi.nlm.nih.gov/24711008/) |  |
| 2 | 4403 | m.4403G\>A | G4403A\-F2 | ND | Mitochondrial Myopathy | ND | ND | 2014 | [24711008](https://pubmed.ncbi.nlm.nih.gov/24711008/) |  |

# **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 | 4403 | m.4403G\>A | G4403A\-F1 | G4403A\-F1\-P1 | De novo | F | Y | Y | A | 61 | 0 | 63% | 0 | / | progressive muscle weakness and atrophy had a muscle biopsy characterized by a combination of dystrophic features |  |
| 2 | 4403 | m.4403G\>A | G4403A\-F1 | G4403A\-F1\-P2 | Uninf | F | N | N | A | ND | 0 | 0 | 0 | / | Healthy |  |
| 3 | 4403 | m.4403G\>A | G4403A\-F1 | G4403A\-F1\-P3 | Uninf | F | N | N | A | ND | 0 | 0 | 0 | / | Healthy |  |
| 4 | 4403 | m.4403G\>A | G4403A\-F2 | G4403A\-F2\-P1 | De novo | F | Y | Y | A | 28 | / | 77% | / | / | unusual dystrophic features on muscle biopsy;exercise intolerance;short stature, diffuse muscle atrophy and weakness,and mild steppage gait |  |

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