T7512C

# **General Information**

| **Position** | **7512** | **Variant** | **m.7512T\>C** | **Locus** | **MT\-TS1** | **RNA** | **tRNA Ser (UCN)** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.7512T\>C** variant in MT\-TS1 has been reported in 4 pedigrees. To date, 18 carriers have been reported. Reported mutation loads ranged from 0% to 100%, with a median of 63% overall; affected carriers showed mutation loads from 24% to 100%, with a median of 89%; unaffected carriers showed mutation loads from 0% to 75%, with a median of 46%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (91%) than in blood (24%). In one unaffected carrier, the mutation was undetectable in blood (0%) but exceeded 20% in hair (46%). The main clinical manifestations among affected carriers included photosensitive myoclonus, mELAS overlap syndrome, MERRF, MELAS, severe hearing loss, basal ganglia, bilateral sensorineural hearing loss, cerebellar calcifications, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 7512 | m.7512T\>C |[ T7512C\-F1 ](https://mitofam.com/doc/780/)| Japan | MERRF/MELAS overlap syndrome | 1 | 1 | 1995 | [7669057](https://pubmed.ncbi.nlm.nih.gov/7669057/) |  |
| 2 | 7512 | m.7512T\>C | [T7512C\-F2](https://mitofam.com/doc/781/) | Germany | Progressive myoclonus epilepsy, deafness | 0 | 2 | 1998 | [9778262](https://pubmed.ncbi.nlm.nih.gov/9778262/) |  |
| 3 | 7512 | m.7512T\>C | [T7512C\-F3 ](https://mitofam.com/doc/782/)| Germany | Progressive myoclonus epilepsy, deafness | 8 | 0 | 1998 | [9778262](https://pubmed.ncbi.nlm.nih.gov/9778262/) |  |
| 4 | 7512 | m.7512T\>C | [T7512C\-F4 ](https://mitofam.com/doc/783/)| Sweden | MELAS | 2 | 0 | 2008 | [17894844](https://pubmed.ncbi.nlm.nih.gov/17894844/) |  |

# **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 | 7512 | m.7512T\>C | T7512C\-F1 | T7512C\-F1\-I2 | Uninf | F | N | Y | A | 55 | 76% | 93% | / | / | MERRF/MELAS overlap syndrome |  |
| 2 | 7512 | m.7512T\>C | T7512C\-F1 | T7512C\-F1\-II1 | Fam | M | N | N | A | 31 | 63% | / | / | / | Healthy |  |
| 3 | 7512 | m.7512T\>C | T7512C\-F1 | T7512C\-F1\-II2 | Fam | F | Y | Y | A | 26 | 87% | / | / | / | MERRF/MELAS overlap syndrome |  |
| 4 | 7512 | m.7512T\>C | T7512C\-F2 | T7512C\-F2\-I2 | Uninf | F | N | Y | A | ND | 40% | / | / | / | Photosensitive myoclonus |  |
| 5 | 7512 | m.7512T\>C | T7512C\-F2 | T7512C\-F2\-II1 | Fam | F | Y | Y | D | 14 | / | 95% | / | / | Photosensitive myoclonus, generalized tonic\-clonic seizures, bilateral sensorineural hearing loss, progressive cerebellar ataxia, dementia, mild glucose intolerance, basal ganglia, cerebellar calcifications |  |
| 6 | 7512 | m.7512T\>C | T7512C\-F2 | T7512C\-F2\-II2 | Fam | F | N | Y | A | ND | 45% | / | / | / | Photosensitive myoclonus |  |
| 7 | 7512 | m.7512T\>C | T7512C\-F3 | T7512C\-F3\-I2 | Uninf | F | N | N | A | ND | 50% | / | / | / | Healthy |  |
| 8 | 7512 | m.7512T\>C | T7512C\-F3 | T7512C\-F3\-II1 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 9 | 7512 | m.7512T\>C | T7512C\-F3 | T7512C\-F3\-II2 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 10 | 7512 | m.7512T\>C | T7512C\-F3 | T7512C\-F3\-II4 | Fam | F | N | N | A | ND | 75% | / | / | / | Healthy |  |
| 11 | 7512 | m.7512T\>C | T7512C\-F3 | T7512C\-F3\-II6 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 12 | 7512 | m.7512T\>C | T7512C\-F3 | T7512C\-F3\-III1 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 13 | 7512 | m.7512T\>C | T7512C\-F3 | T7512C\-F3\-III2 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 14 | 7512 | m.7512T\>C | T7512C\-F3 | T7512C\-F3\-III3 | Fam | M | N | N | A | ND | 30% | / | / | / | Healthy |  |
| 15 | 7512 | m.7512T\>C | T7512C\-F3 | T7512C\-F3\-III4 | Fam | M | Y | Y | A | 6 | 1 | 1 | / | / | Severe hearing loss, myoclonic jerks, dystonic posturing, inability to walk, marked psychomotor retardation, loss of acquired skills |  |
| 16 | 7512 | m.7512T\>C | T7512C\-F4 | T7512C\-F4\-I2 | Uninf | F | N | N | A | ND | 35% | / | / | / | Healthy |  |
| 17 | 7512 | m.7512T\>C | T7512C\-F4 | T7512C\-F4\-II1 | Fam | F | Y | Y | A | 4 | 24% | 91% | / | / | MELAS |  |
| 18 | 7512 | m.7512T\>C | T7512C\-F4 | T7512C\-F4\-II2 | Fam | F | N | N | A | ND | 0 | / | / | 46% (H) | Healthy |  |

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