T3291C

# **General Information**

| **Position** | **3291** | **Variant** | **m.3291T\>C** | **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.3291T\>C** variant in MT\-TL1 has been reported in 6 pedigrees. To date, 20 carriers have been reported. Reported mutation loads ranged from 6% to 95%, with a median of 46% overall; affected carriers showed mutation loads from 11% to 95%, with a median of 50%; unaffected carriers showed mutation loads from 6% to 50%, with a median of 32\.5%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (86%) than in blood (30%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (95%) than in blood (40%). Similar tissue\-specific differences were observed in 1 additional carriers. The main clinical manifestations among affected carriers included dysarthria, glaucoma, hearing loss, deafness, isolated mild myopathy, loss of consciousness, MELAS, mELAS overlap syndrome, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3291 | m.3291T\>C | T3291C\-F1 | Japan | MELAS | 0 | 0 | 1994 | [7520241](https://pubmed.ncbi.nlm.nih.gov/7520241/) |  |
| 2 | 3291 | m.3291T\>C | [T3291C\-F2](https://mitofam.com/doc/2316/) | Italy | Neuromuscular syndrome | 2 | 0 | 2000 | [10899447](https://pubmed.ncbi.nlm.nih.gov/10899447/) |  |
| 3 | 3291 | m.3291T\>C | T3291C\-F3 | Italy | Progressive cognitive, behavioral decline, hearing loss | 0 | 0 | 2011 | [20943236](https://pubmed.ncbi.nlm.nih.gov/20943236/) |  |
| 4 | 3291 | m.3291T\>C | [T3291C\-F4](https://mitofam.com/doc/2317/) | Japan | Encephalomyopathy | 4 | 4 | 2011 | [21863273](https://pubmed.ncbi.nlm.nih.gov/21863273/) |  |
| 5 | 3291 | m.3291T\>C | [T3291C\-F5](https://mitofam.com/doc/2318/) | UK | Deafness, falls, speech disturbance, weight loss, macroglossia, dysarthria, pes cavus, dorsocervical fat pad, lipoma, reduced muscle bulk, mild proximal muscle weakness, suppressed limb reflexes, reduced dorsal column sensation at toes and ankles, limb dysmetria, broad\-based gait, inability to perform tandem gait, generalised brain atrophy, fatty tongue infiltration, active denervation in lower limbs and right bicep, reduced muscle recruitment | 2 | 0 | 2013 | [23273904](https://pubmed.ncbi.nlm.nih.gov/23273904/) |  |
| 6 | 3291 | m.3291T\>C | [T3291C\-F6](https://mitofam.com/doc/2319/) | China | MERRF/MELAS overlap syndrome | 2 | 0 | 2014 | [24338029](https://pubmed.ncbi.nlm.nih.gov/24338029/) |  |

# **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 | 3291 | m.3291T\>C | T3291C\-F1 | T3291C\-F1\-II1 | De novo | M | Y | Y | A | 7 | 30% | 86% | / | / | MELAS |  |
| 2 | 3291 | m.3291T\>C | T3291C\-F2 | T3291C\-F2\-I2 | De novo | F | N | N | A | ND | 19% | / | / | / | Healthy |  |
| 3 | 3291 | m.3291T\>C | T3291C\-F2 | T3291C\-F2\-II1 | Fam | F | Y | Y | A | 7\.6 | 45% | 87% | / | 50% (F) | Isolated mild myopathy |  |
| 4 | 3291 | m.3291T\>C | T3291C\-F2 | T3291C\-F2\-II2 | Fam | M | N | N | A | ND | 6% | / | / | / | Healthy |  |
| 5 | 3291 | m.3291T\>C | T3291C\-F3 | T3291C\-F3\-II1 | De novo | F | Y | Y | A | 23 | 40% | \>95% | / | / | Progressive cognitive, behavioral decline, hearing loss |  |
| 6 | 3291 | m.3291T\>C | T3291C\-F4 | T3291C\-F4\-I2 | Uninf | F | N | Y | D | 80 | / | / | / | / | Hearing loss, glaucoma, progressive bedridden state |  |
| 7 | 3291 | m.3291T\>C | T3291C\-F4 | T3291C\-F4\-II1 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 8 | 3291 | m.3291T\>C | T3291C\-F4 | T3291C\-F4\-II2 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 9 | 3291 | m.3291T\>C | T3291C\-F4 | T3291C\-F4\-II4 | Fam | F | Y | Y | A | 45 | 11% | 74% | / | / | Progressive gait disturbance, bilateral hearing deficits, cataracts, glaucoma, mild external ophthalmoparesis, nystagmus, sensorineural hearing loss, dysarthria, severe cerebellar ataxia, mild proximal limb weakness, reduced tendon reflexes, diffuse paroxysmal slow activity induced by photo\-stimulation, low amplitude and short motor\-unit potential in proximal extremities, frontal lobe and cerebellar cortex atrophy, impaired intelligence, memory and frontal function |  |
| 10 | 3291 | m.3291T\>C | T3291C\-F4 | T3291C\-F4\-II5 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 11 | 3291 | m.3291T\>C | T3291C\-F4 | T3291C\-F4\-III2 | Fam | F | N | Y | A | 41 | / | / | / | / | Palindromic rheumatism, recurrent migraine |  |
| 12 | 3291 | m.3291T\>C | T3291C\-F4 | T3291C\-F4\-III3 | Fam | F | N | Y | A | 36 | 16% | / | / | / | Photo\-induced myoclonus, negative myoclonus, absence of all limb tendon reflexes, mild truncal ataxia, cerebellar atrophy |  |
| 13 | 3291 | m.3291T\>C | T3291C\-F4 | T3291C\-F4\-IV1 | Fam | F | N | Y | A | 15 | 27% | / | / | / | Loss of consciousness, myoclonic jerks, generalized seizure, absent tendon reflexes, and slight cognitive decline. |  |
| 14 | 3291 | m.3291T\>C | T3291C\-F4 | T3291C\-F4\-IV2 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 15 | 3291 | m.3291T\>C | T3291C\-F5 | T3291C\-F5\-I2 | Uninf | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 16 | 3291 | m.3291T\>C | T3291C\-F5 | T3291C\-F5\-II1 | Fam | M | Y | Y | A | 55 | / | 39% | / | / | Deafness, falls, speech disturbance, weight loss, macroglossia, dysarthria, pes cavus, dorsocervical fat pad, lipoma, reduced muscle bulk, mild proximal muscle weakness, suppressed limb reflexes, reduced dorsal column sensation at toes and ankles, limb dysmetria, broad\-based gait, inability to perform tandem gait, generalised brain atrophy, fatty tongue infiltration, active denervation in lower limbs and right bicep, reduced muscle recruitment |  |
| 17 | 3291 | m.3291T\>C | T3291C\-F5 | T3291C\-F5\-II2 | Fam | F | N | N | A | ND | \+ | \+ | / | / | Healthy |  |
| 18 | 3291 | m.3291T\>C | T3291C\-F6 | T3291C\-F6\-I2 | Uninf | F | N | N | A | 48 | 46% | / | / | / | Healthy |  |
| 19 | 3291 | m.3291T\>C | T3291C\-F6 | T3291C\-F6\-II1 | Fam | F | Y | Y | A | 14 | 67% | 93% | / | 62% (F) | MERRF/MELAS overlap syndrome |  |
| 20 | 3291 | m.3291T\>C | T3291C\-F6 | T3291C\-F6\-II2 | Fam | F | N | N | A | 2\.5 | 50% | / | / | / | Healthy |  |

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