G586A

# **General Information**

| **Position** | **586** | **Variant** | **m.586G\>A** | **Locus** | **MT\-TF** | **RNA** | **tRNA Phe** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | 89\.70% | **Pathogenicity** | Reported \[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.586G\>A** variant in MT\-TF has been reported in 2 pedigrees. To date, 4 carriers have been reported. Reported mutation loads ranged from 3% to 90%, with a median of 29% overall; affected carriers showed mutation loads from 3% to 90%, with a median of 34\.5%; unaffected carriers showed mutation loads from 13%, with a median of 13%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (85%) and urine (29%) than in blood (3%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (90%) and urine (40%) than in blood (4%). The main clinical manifestations among affected carriers included akinesia\-rigidity, non\-progressive muscle weakness and myalgia, abdominal pain, abnormal movements, and profound sensorineural deafness, dementia, fatigue, headache and vomiting after exertion, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 586 | m.586G\>A | [G586A\-F1](https://mitofam.com/doc/982/) | UK | Progressive neurodegenerative disorder with psychiatric disturbance, dementia, and akinesia\-rigidity | 2 | 0 | 2010 | 21060018 |  |
| 2 | 586 | m.586G\>A | G586A\-F2 | France | Mitochondrial myopathy | 0 | 0 | 2019 | 31463198 |  |

# **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 | 586 | m.586G\>A | G586A\-F1 | G586A\-F1\-I2 | Uninf | F | N | N | D | 80 | / | / | / | 13% (Breast) | Healthy |  |
| 2 | 586 | m.586G\>A | G586A\-F1 | G586A\-F1\-II2 | Fam | F | Y | Y | A | 57 | 3% | 85% | 29% | / | Akinesia\-rigidity, abnormal movements, dementia, psychiatric disturbance, and profound sensorineural deafness |  |
| 3 | 586 | m.586G\>A | G586A\-F1 | G586A\-F1\-III1 | Fam | M | N | N | A | 20 | / | / | / | / | Healthy |  |
| 4 | 586 | m.586G\>A | G586A\-F2 | G586A\-F2\-P1 | De novo | M | Y | Y | A | 14 | 4% | \>90% | 40% | / | Non\-progressive muscle weakness and myalgia; fatigue, night cramps, abdominal pain, headache and vomiting after exertion; mitochondrial myopathy |  |

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