T13094C

# **General Information**

| **Position** | **13094** | **Variant** | **m.13094T\>C** | **Locus** | **MT\-ND5** | **Amino\-AcidChange** | **V253A** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | Likely\-pathogenic | **Pathogenicity** | Cfrm \[P] |

"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.13094T\>C** variant in MT\-ND5 has been reported in 19 pedigrees. To date, 30 carriers have been reported. Reported mutation loads ranged from 0% to 94%, with a median of 39% overall; affected carriers showed mutation loads from 0% to 94%, with a median of 49%; unaffected carriers showed mutation loads from 0% to 45%, with a median of 7%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in blood (50%) than in blood (3%). In one affected carrier, the mutation was undetectable in blood (0%) but exceeded 20% in urine (55%). Similar tissue\-specific differences were observed in 5 additional carriers. The main clinical manifestations among affected carriers included leigh syndrome, MELAS, deceased., LHON, leigh, SCA, ataxia., ataxic\-spastic gait, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 13094 | m.13094T\>C | T13094C\-F1 | Italy | Mitochondrial encephalomyopathy | 0 | 0 | 2009 | [18977334](https://pubmed.ncbi.nlm.nih.gov/18977334/) | Familial carriers were not identified among tested maternal relatives.; Patient 2 family; Patient 2 clinical description and heteroplasmy/relative testing text.; Italy; patients investigated at Italian mitochondrial center |
| 2 | 13094 | m.13094T\>C | T13094C\-F2 | Australia inferred | Leigh syndrome | 0 | 0 | 2011 | [21364701](https://pubmed.ncbi.nlm.nih.gov/21364701/) | m.13094T\>C LS proband; Table 1; Australia; Melbourne pediatric/diagnostic cohort inferred from affiliations and cohort source. |
| 3 | 13094 | m.13094T\>C | T13094C\-F3 | United Kingdom | MELAS/Leigh disease with cerebellar ataxia | 0 | 0 | 2012 | [22249460](https://pubmed.ncbi.nlm.nih.gov/22249460/) | Clinicopathological brain tissue cohort; no family details.; Brain tissue cohort Patient 10; Patient table lists mutation and diagnosis.; United Kingdom brain bank/clinicopathological cohort |
| 4 | 13094 | m.13094T\>C | T13094C\-F4 | United Kingdom | MELAS/Leigh disease | 0 | 0 | 2012 | [22577219](https://pubmed.ncbi.nlm.nih.gov/22577219/) | Patient 11; Page 3 Table 1: Pt11 genotype m.13094T\>C, age at death 34, female, diagnosis MELAS/Leigh disease.; United Kingdom inferred from Newcastle mitochondrial disease/autopsy cohort context. |
| 5 | 13094 | m.13094T\>C | T13094C\-F5 | Japan | Leigh syndrome or Leigh\-like syndrome | 0 | 0 | 2017 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) | Pedigree/table recheck retained only Pt153 for T13094C; Pt467 and Pt744 were removed because Table 4 lists them as m.13513G\>A. |
| 6 | 13094 | m.13094T\>C | [T13094C\-F6](https://mitofam.com/doc/1377/) | Spain | LHON | 1 | 0 | 2018 | [29479304](https://pubmed.ncbi.nlm.nih.gov/29479304/) | mother is low\-level urine carrier despite blood negative.; Childhood\-onset LHON family; pages 2\-3; Spanish case report / Barcelona\-Zaragoza affiliations |
| 7 | 13094 | m.13094T\>C | [T13094C\-F7](https://mitofam.com/doc/1378/) | international | LHON/MELAS/Leigh spectrum | 0 | 2 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 1; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 8 | 13094 | m.13094T\>C | [T13094C\-F8](https://mitofam.com/doc/1379/) | international | SCA/MELAS/Leigh\-like spectrum | 0 | 2 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | P2\.2 had blood 0 and P2\.3 was not sampled, so neither is filled as carrier.; Family 2; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 9 | 13094 | m.13094T\>C | [T13094C\-F9](https://mitofam.com/doc/1380/) | international | Leigh syndrome | 1 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 3; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 10 | 13094 | m.13094T\>C |[ T13094C\-F10](https://mitofam.com/doc/1381/) | international | Leigh syndrome with cardiomyopathy | 1 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 4; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 11 | 13094 | m.13094T\>C | T13094C\-F11 | international | MELAS/Leigh syndrome | 0 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 5; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 12 | 13094 | m.13094T\>C | T13094C\-F12 | international | Leigh syndrome | 0 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 6; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 13 | 13094 | m.13094T\>C |[ T13094C\-F13](https://mitofam.com/doc/1382/) | international | LHON/subclinical optic neuropathy | 1 | 1 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 7; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 14 | 13094 | m.13094T\>C |[ T13094C\-F14](https://mitofam.com/doc/1383/) | international | MELAS/Leigh syndrome | 1 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 8; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 15 | 13094 | m.13094T\>C | T13094C\-F15 | international | MELAS | 0 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 9; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 16 | 13094 | m.13094T\>C | T13094C\-F16 | international | Leigh syndrome | 0 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 10; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 17 | 13094 | m.13094T\>C | T13094C\-F17 | international | Leigh syndrome | 0 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 11; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 18 | 13094 | m.13094T\>C | T13094C\-F18 | international | Leigh syndrome | 0 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 12; Tables 1\-2; International cohort; individual country not consistently stated in main text. |
| 19 | 13094 | m.13094T\>C | T13094C\-F19 | international | Leigh syndrome | 0 | 0 | 2018 | [29506874](https://pubmed.ncbi.nlm.nih.gov/29506874/) | Family 13; Tables 1\-2; International cohort; individual country not consistently stated in main text. |

# **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 | 13094 | m.13094T\>C | T13094C\-F1 | T13094C\-F1\-P1 | Uninf | F | Y | Y | A | 11 | 40% | 50% | / | 30%(F) | Ataxic\-spastic gait; CPEO; facial weakness; drooling; dysphagia; seizures; severe growth and mental retardation; hearing loss | Age 11 at report; onset around age 7\.; Case 2 text reports lymphocyte, muscle, and fibroblast heteroplasmy.; Source: Patient 2 |
| 2 | 13094 | m.13094T\>C | T13094C\-F2 | T13094C\-F2\-P1 | Uninf | ND | Y | Y | A | ND | / | \~60% | / | / | Leigh syndrome | Table 1; Source: LS proband; Complex I deficiency. |
| 3 | 13094 | m.13094T\>C | T13094C\-F3 | T13094C\-F3\-P1 | Uninf | F | Y | Y | D | 34 | / | / | / | Positive(Brain/tissue) | Cerebellar ataxia; MELAS/Leigh disease diagnosis | Brain donor/pathology cohort.; Clinical molecular table.; Source: Patient 10 |
| 4 | 13094 | m.13094T\>C | T13094C\-F4 | T13094C\-F4\-P1 | Uninf | F | Y | Y | D | 34 y at death | / | / | / | / | MELAS/Leigh disease, myoclonus, fatigue; disease duration 2 y | Mutation quantified methods described, but patient\-specific load not reported in Table 1\.; Page 3 Table 1\.; Source: Patient 11 |
| 5 | 13094 | m.13094T\>C | T13094C\-F5 | T13094C\-F5\-P1 | Uninf | ND | Y | Y | ND | ND | Het | Het | / | / | Leigh syndrome | Table lists tissues B,M and heteroplasmy not available.; Table 4\.; Source: Pt153; Combined complex I/IV deficiency. |
| 6 | 13094 | m.13094T\>C | T13094C\-F6 | T13094C\-F6\-II1 | Fam | M | Y | Y | A | 10 | 50% initially; undetectable after 3 years | / | / | Positive(ND) | bilateral painless visual loss; childhood\-onset LHON; spontaneous visual recovery | younger brother blood/urine negative; mother blood negative and urine 10%; case report and Fig. 2; Source: patient |
| 7 | 13094 | m.13094T\>C | T13094C\-F6 | T13094C\-F6\-I2 | Fam | F | N | N | ND | ND | 0%/not found in blood | / | 10% | / | Healthy | low\-level urine carrier; Fig. 2B; Source: mother; Affected status not reported beyond asymptomatic/not reported affected. |
| 8 | 13094 | m.13094T\>C | T13094C\-F6 | T13094C\-F6\-II2 | Fam | M | N | ND | ND | ND | 0% | / | 0% | / | ND | Younger brother blood and urine negative; mother urine 10% positive and blood negative; included per new skill rule for negative\-tested maternal\-line descendant.; No target mutation detected in blood or urine; phenotype not reported. |
| 9 | 13094 | m.13094T\>C | T13094C\-F7 | T13094C\-F7\-I2 | Uninf | F | Y | Y | D | 37 years | 0% | / | 55% | / | LHON/MELAS; onset 17 years; deceased. | P1 |
| 10 | 13094 | m.13094T\>C | T13094C\-F7 | T13094C\-F7\-II1 | Fam | M | N | Y | D | 9 months | / | 65% | / | / | Leigh syndrome; onset 2 months; deceased. | P1\.1 |
| 11 | 13094 | m.13094T\>C | T13094C\-F7 | T13094C\-F7\-II2 | Fam | F | N | Y | D | 14 years | 46% | 90% | 67% | / | MELAS/Leigh; onset 10 years; deceased. | P1\.2 |
| 12 | 13094 | m.13094T\>C | T13094C\-F8 | T13094C\-F8\-III1 | Fam | F | Y | Y | A | 30 years | 94% | 35% | 0% | / | SCA/MELAS; onset 12 years. | P2 |
| 13 | 13094 | m.13094T\>C | T13094C\-F8 | T13094C\-F8\-II1 | Fam | F | N | Y | A | 49 years | 3% | / | 22% | / | Ataxia. | P2\.1 |
| 14 | 13094 | m.13094T\>C | T13094C\-F8 | T13094C\-F8\-III2 | Fam | M | N | Y | A | 43 years | 29% | / | / | / | Leigh\-like/SCA; onset 5 years. | P2\.4 |
| 15 | 13094 | m.13094T\>C | T13094C\-F9 | T13094C\-F9\-II1 | Fam | M | Y | Y | D | 5\.4 months | 76% | 80% | 81% | / | Leigh syndrome; onset 6 weeks; deceased. | Table 1/2; Source: P3 |
| 16 | 13094 | m.13094T\>C | T13094C\-F9 | T13094C\-F9\-I2 | Fam | F | N | N | A | 20s | 19% | / | 45% | / | Healthy | Table 1/2; Source: P3\.1 mother |
| 17 | 13094 | m.13094T\>C | T13094C\-F10 | T13094C\-F10\-II1 | Fam | M | Y | Y | D | 6 years | / | 71% | / | / | Leigh syndrome, hypertrophic cardiomyopathy and spasticity; onset 4 years; deceased. | Table 1/2; Source: P4 |
| 18 | 13094 | m.13094T\>C | T13094C\-F10 | T13094C\-F10\-I2 | Fam | F | N | N | A | ND | 4% | / | 9% | / | Healthy | Table 1/2; Source: P4\.1 mother |
| 19 | 13094 | m.13094T\>C | T13094C\-F11 | T13094C\-F11\-P1 | Uninf | F | Y | Y | D | 14 years | / | 28% | / | / | MELAS/Leigh with myoclonus; onset 13 years; deceased. | Table 1/2; Source: P5 |
| 20 | 13094 | m.13094T\>C | T13094C\-F12 | T13094C\-F12\-P1 | Uninf | M | Y | Y | A | 3 years | 45% | 58% | / | / | Leigh syndrome with bradycardia; onset 2\.25 years. | Table 1/2; Source: P6 |
| 21 | 13094 | m.13094T\>C | T13094C\-F13 | T13094C\-F13\-II1 | Fam | M | Y | Y | A | 21 years | 26% | / | / | / | LHON; onset 7 years. | Table 1/2; Source: P7 |
| 22 | 13094 | m.13094T\>C | T13094C\-F13 | T13094C\-F13\-II2 | Fam | M | N | Y | A | 20 years | 35% | / | / | / | Subclinical optic neuropathy; onset 6 years. | Table 1/2; Source: P7\.1 |
| 23 | 13094 | m.13094T\>C | T13094C\-F13 | T13094C\-F13\-I2 | Fam | F | N | N | A | 47 years | 7% | / | / | / | Healthy | Table 1/2; Source: P7\.2 mother |
| 24 | 13094 | m.13094T\>C | T13094C\-F14 | T13094C\-F14\-II1 | Fam | F | Y | Y | D | 35 years | / | 83% | / | / | MELAS/Leigh, patent foramen ovale and myoclonus; onset 34 years; deceased. | Table 1/2; Source: P8 |
| 25 | 13094 | m.13094T\>C | T13094C\-F14 | T13094C\-F14\-I2 | Fam | F | N | N | A | 70s | 0% | / | 6% | / | Healthy | Table 1/2; Source: P8\.1 mother; Mutation positive only in urine. |
| 26 | 13094 | m.13094T\>C | T13094C\-F15 | T13094C\-F15\-P1 | Uninf | F | Y | Y | A | 34 years | 5% | 80% | / | / | MELAS; onset 27 years. | Table 1/2; Source: P9 |
| 27 | 13094 | m.13094T\>C | T13094C\-F16 | T13094C\-F16\-P1 | Uninf | M | Y | Y | A | 24 years | 38% | 61% | / | / | Leigh syndrome, left ventricular hypertrophy, non\-invasive ventilation, bilateral INO; onset 22 years. | Table 1/2; Source: P10 |
| 28 | 13094 | m.13094T\>C | T13094C\-F17 | T13094C\-F17\-P1 | Uninf | M | Y | Y | A | 30 years | / | / | / | Positive(ND) | Leigh syndrome, raised CSF lactate, PEG, dystonia, tracheostomy and facial weakness; onset 2 years. | Exact tissue and load absent from local table/text.; Table 1/2; Source: P11 |
| 29 | 13094 | m.13094T\>C | T13094C\-F18 | T13094C\-F18\-P1 | Uninf | M | Y | Y | A | 4 years | / | / | / | 41%(F) | Leigh syndrome; onset 1 year. | Table 1/2; Source: P12 |
| 30 | 13094 | m.13094T\>C | T13094C\-F19 | T13094C\-F19\-P1 | Uninf | M | Y | Y | D | 14 years | 49% | 52% | / | / | Leigh syndrome with tracheostomy and PEG; onset 1 year; deceased. | Table 1/2; Source: P13 |

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