A3251G

# **General Information**

| **Position** | **3251** | **Variant** | **m.3251A\>G** | **Locus** | **MT\-TL1** | **RNA** | **tRNA Leu (UUR)** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.3251A\>G** variant in MT\-TL1 has been reported in 3 pedigrees. To date, 17 carriers have been reported. Reported mutation loads ranged from 13% to 94%, with a median of 79% overall; affected carriers showed mutation loads from 13% to 94%, with a median of 79%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (81%) than in blood (13%). The main clinical manifestations among affected carriers included early death, myopathy, diarrhoea, MELAS, brain oedema, bronchitis and liver congestion., cardiorespiratory failure, exercise intolerance, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3251 | m.3251A\>G | [A3251G\-F1](https://mitofam.com/doc/2230/) | UK | Ocular, neck and proximal upper limb weakness, psychiatric features, sudden death | 0 | 14 | 1993 | [8265770](https://pubmed.ncbi.nlm.nih.gov/8265770/) |  |
| 2 | 3251 | m.3251A\>G | A3251G\-F2 | Sweden | Diarrhoea, nausea, fatigue, tachycardia, exercise intolerance, severe muscle weakness and wasting, lactic acidosis, hypercapnia, hypoventilation, cardiorespiratory failure, brain oedema, global ischemia, right ventricular hypertrophy atelectasis, bronchitis and liver congestion. | ND | ND | 1996 | [8786060](https://pubmed.ncbi.nlm.nih.gov/8786060/) |  |
| 3 | 3251 | m.3251A\>G | A3251G\-F3 | India | MELAS | ND | ND | 2019 | [30837005](https://pubmed.ncbi.nlm.nih.gov/30837005/) |  |

# **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 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-I1 | Uninf | F | N | Y | D | 50 | / | / | / | / | Early death |  |
| 2 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-I2 | Uninf | F | N | Y | D | 50 | / | / | / | / | Early death |  |
| 3 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-I3 | Uninf | F | N | Y | D | 50 | / | / | / | / | Myopathy, early death |  |
| 4 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-I4 | Uninf | F | N | Y | D | 4\~15 | / | / | / | / | Early death |  |
| 5 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-I5 | Uninf | M | N | Y | D | 20 | / | / | / | / | Myopathy, early death |  |
| 6 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-I6 | Uninf | M | N | Y | D | 20 | / | / | / | / | Early death |  |
| 7 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-II1 | Fam | M | N | Y | A | 20 | 21% | / | / | / | Myopathy |  |
| 8 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-II2 | Fam | F | N | Y | D | 36 | / | / | / | / | Myopathy, early death |  |
| 9 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-II3 | Fam | F | Y | Y | A | 20 | 13% | 81% | / | / | Myopathy |  |
| 10 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-II4 | Fam | F | N | Y | D | 30 | / | / | / | / | Early death |  |
| 11 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-II5 | Fam | M | N | Y | D | 16 | / | / | / | / | Myopathy, early death |  |
| 12 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-II6 | Fam | M | N | Y | D | 25 | / | / | / | / | Myopathy, early death |  |
| 13 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-II7 | Fam | F | N | Y | A | ND | 16% | / | / | / | Myopathy |  |
| 14 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-II8 | Fam | M | N | Y | D | 21 | / | / | / | / | Myopathy, early death |  |
| 15 | 3251 | m.3251A\>G | A3251G\-F1 | A3251G\-F1\-III3 | Fam | M | N | Y | A | 4 | 25% | / | / | / | Myopathy |  |
| 16 | 3251 | m.3251A\>G | A3251G\-F2 | A3251G\-F2\-P1 | Uninf | F | Y | Y | D | 13 | / | 94% | / | 93% (F), 79% (Heart), 80% (Liver), 90% (Brain) | Diarrhoea, nausea, fatigue, tachycardia, exercise intolerance, severe muscle weakness and wasting, lactic acidosis, hypercapnia, hypoventilation, cardiorespiratory failure, brain oedema, global ischemia, right ventricular hypertrophy atelectasis, bronchitis and liver congestion. |  |
| 17 | 3251 | m.3251A\>G | A3251G\-F3 | A3251G\-F3\-P1 | Uninf | M | Y | Y | A | 14 | 70% | / | / | / | MELAS |  |

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