T13046C

# **General Information**

| **Position** | **13046** | **Variant** | **m.13046T\>C** | **Locus** | **MT\-ND5** | **Amino\-AcidChange** | **M237T** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **APOGEE2** | 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.13046T\>C** variant in MT\-ND5 has been reported in 4 pedigrees. To date, 4 carriers have been reported. Reported mutation loads ranged from 22% to 82\.7%, with a median of 44% overall; affected carriers showed mutation loads from 22% to 82\.7%, with a median of 44%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (50%) and urine (52%) than in blood (22%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (70%) and urine (71%) than in blood (27%). Similar tissue\-specific differences were observed in 1 additional carriers. The main clinical manifestations among affected carriers included abrupt painless bilateral vision loss, lHON\-like then multisystem disease, lactic acidosis, leigh syndrome, optic neuropathy, sSVs, visual loss, anhedonia, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 13046 | m.13046T\>C | T13046C\-F1 | China | MELAS/Leigh overlap | 0 | 0 | 2011 | [21850008](https://pubmed.ncbi.nlm.nih.gov/21850008/) | Maternal carrier not detected.; Patient 1 family; Patient 1 clinical and heteroplasmy text.; China; Chinese MELAS cohort |
| 2 | 13046 | m.13046T\>C | T13046C\-F2 | Czech Republic | LHON/MELAS overlap | 0 | 0 | 2016 | [26894521](https://pubmed.ncbi.nlm.nih.gov/26894521/) | Czech family; Case report and family testing.; Czech Republic; Czech clinical/genetic center. |
| 3 | 13046 | m.13046T\>C | T13046C\-F3 | Czech Republic | LHON/MELAS overlap | 0 | 0 | 2020 | [31996177](https://pubmed.ncbi.nlm.nih.gov/31996177/) | P7 family; Table 1\.; Czech Republic inferred from Czech diagnostic center and patient cohort context. |
| 4 | 13046 | m.13046T\>C | T13046C\-F4 | USA | Leigh syndrome | 0 | 0 | 2022 | [34969639](https://pubmed.ncbi.nlm.nih.gov/34969639/) | Kindred 28; Table 1\.; USA; CHOP/US diagnostic cohort. |

# **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 | 13046 | m.13046T\>C | T13046C\-F1 | T13046C\-F1\-P1 | Uninf | F | Y | Y | A | 13 | 22% | 50% | 52% | / | Visual loss; ataxia; seizures; right homonymous hemianopia; short stature; brain lesions; SSVs | Onset at age 6; healthy mother tested negative.; Case text and heteroplasmy values.; Source: Patient 1 |
| 2 | 13046 | m.13046T\>C | T13046C\-F2 | T13046C\-F2\-P1 | De novo | F | Y | Y | A | 12 y | 27% | 70% | 71% | 44%(H); 40%(F); 34%(BM) | Abrupt painless bilateral vision loss, hearing loss, vertigo, migraines, anhedonia, thyroiditis, optic atrophy, elevated CSF lactate, mitochondrial myopathy | Case report and mutation\-load table.; Source: Patient |
| 3 | 13046 | m.13046T\>C | T13046C\-F3 | T13046C\-F3\-P1 | Uninf | ND | Y | Y | A | onset 12 y; alive 17 y | 27% | 70% | 71% | 43%(F); 44%(H); 34%(BM) | Optic neuropathy; LHON\-like then multisystem disease | Table 1\.; Source: P7 |
| 4 | 13046 | m.13046T\>C | T13046C\-F4 | T13046C\-F4\-P1 | Uninf | ND | Y | Y | A | 0\.8 y at tissue collection | / | / | / | 82\.7%(F) | Lactic acidosis, developmental delay, Leigh syndrome | Maternal tissue testing ND.; Table 1\.; Source: Case 33 |

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