G12147A

# **General Information**

| **Position** | **12147** | **Variant** | **m.12147G\>A** | **Locus** | **MT\-TH** | **RNA** | **tRNA His** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | Pathogenic | **Pathogenicity** | Cfrm \[LP] |

"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.12147G\>A** variant in MT\-TH has been reported in 2 pedigrees. To date, 3 carriers have been reported. Reported mutation loads ranged from 0% to 86%, with a median of 1% overall; affected carriers showed mutation loads from 0% to 86%, with a median of 29%; unaffected carriers showed mutation loads from 0%, with a median of 0%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (81%) than in blood (25%). In one affected carrier, the mutation was undetectable in hair (0%) but exceeded 20% in muscle (86%) and urine (33%). The main clinical manifestations among affected carriers included headache, MELAS, MERFF, bilateral optic atrophy, cognitive impairment, proximal limb weakness, seizures, severe cerebral edema, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 12147 | m.12147G\>A | [G12147A\-F1 ](https://mitofam.com/doc/587/)| Italy | MELAS/MERFF | 1 | 1 | 2004 | [14967777](https://pubmed.ncbi.nlm.nih.gov/14967777/) |  |
| 2 | 12147 | m.12147G\>A | G12147A\-F2 | UK | Headache, seizures, severe cerebral edema, cognitive impairment, slight right\-sided ptosis, bilateral optic atrophy, proximal limb weakness | 0 | 0 | 2004 | [15111688](https://pubmed.ncbi.nlm.nih.gov/15111688/) |  |

# **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 | 12147 | m.12147G\>A | G12147A\-F1 | G12147A\-F1\-III1 | Fam | M | Y | Y | A | 25 | 25% | 81% | / | / | MELAS/MERFF |  |
| 2 | 12147 | m.12147G\>A | G12147A\-F1 | G12147A\-F1\-III2 | Fam | F | N | N | A | ND | 0 | / | 0 | 0% (H) | Healthy |  |
| 3 | 12147 | m.12147G\>A | G12147A\-F2 | G12147A\-F2\-P1 | De novo | M | Y | Y | A | 22 | 1% | 86% | 33% | 0% (H) | Headache, seizures, severe cerebral edema, cognitive impairment, slight right\-sided ptosis, bilateral optic atrophy, proximal limb weakness |  |

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