C3303T

# **General Information**

| **Position** | **3303** | **Variant** | **m.3303C\>T** | **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.3303C\>T** variant in MT\-TL1 has been reported in 10 pedigrees. To date, 46 carriers have been reported. Homoplasmy was reported in 3/46 carriers (6\.5%), and 24/46 carriers (52\.2%) were affected. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in heart (98%) than in muscle (35%). The main clinical manifestations among affected carriers included cardiomyopathy, skeletal myopathy, congestive heart failur, myopathy, psychiatric illness characterized by psychoses and recurrent episodes of depression, short stature, lactic acidosis, early dementia, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3303 | m.3303C\>T | C3303T\-F1 | USA | Cardiomyopathy | 7 | 6 | 1994 | [7906985](https://pubmed.ncbi.nlm.nih.gov/7906985/) |  |
| 2 | 3303 | m.3303C\>T | C3303T\-F2 | USA | Cardiomyopathy | 3 | 0 | 1999 | [9841711](https://pubmed.ncbi.nlm.nih.gov/9841711/) |  |
| 3 | 3303 | m.3303C\>T | C3303T\-F3 | USA | Infantile cardiomyopathy | 3 | 0 | 1999 | [10431114](https://pubmed.ncbi.nlm.nih.gov/10431114/) |  |
| 4 | 3303 | m.3303C\>T | C3303T\-F4 | Australia | Proximal limb and neck weakness, cardiac dysfunction | 3 | 0 | 1999 | [10431114](https://pubmed.ncbi.nlm.nih.gov/10431114/) |  |
| 5 | 3303 | m.3303C\>T | C3303T\-F5 | Chile | Skeletal myopathy, cardiomyopathy | 0 | 3 | 1999 | [10431114](https://pubmed.ncbi.nlm.nih.gov/10431114/) |  |
| 6 | 3303 | m.3303C\>T | C3303T\-F6 | Japan | Infantile cardiomyopathy, skeletal myopathy, cardiomyopathy | 3 | 1 | 1999 | [10431114](https://pubmed.ncbi.nlm.nih.gov/10431114/) |  |
| 7 | 3303 | m.3303C\>T | C3303T\-F7 | Spain | Myopathy, cardiomyopathy, psychiatric illness | 2 | 4 | 2001 | [11768589](https://pubmed.ncbi.nlm.nih.gov/11768589/) |  |
| 8 | 3303 | m.3303C\>T | C3303T\-F8 | Czech Republic | Hypertrophic cardiomyopathy | ND | ND | 2012 | [23258140](https://pubmed.ncbi.nlm.nih.gov/23258140/) |  |
| 9 | 3303 | m.3303C\>T | C3303T\-F9 | China | Myopathy | ND | ND | 2020 | [33013660](https://pubmed.ncbi.nlm.nih.gov/33013660/) |  |
| 10 | 3303 | m.3303C\>T | C3303T\-F10 | China | Myopathy | ND | ND | 2020 | [33013660](https://pubmed.ncbi.nlm.nih.gov/33013660/) |  |

# **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 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-I1 | Uninf | F | N | N | D | ND | / | / | / | / | Healthy |  |
| 2 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-II1 | Fam | F | N | N | D | 50 | / | / | / | / | Healthy |  |
| 3 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-II3 | Fam | M | N | Y | D | 17 | / | / | / | / | Myocardial infarction |  |
| 4 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-III2 | Fam | M | N | Y | D | 50 | / | / | / | / | Cardiomyopathy |  |
| 5 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-III3 | Fam | F | N | Y | A | ND | 28% | / | / | / | Cardiomyopathy |  |
| 6 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-III5 | Fam | F | N | N | D | 63 | / | / | / | / | Healthy |  |
| 7 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-IV2 | Fam | M | N | N | A | 45 | 9% | / | / | / | Healthy |  |
| 8 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-IV3 | Fam | F | N | N | A | 40 | 11% | / | / | / | Healthy |  |
| 9 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-IV5 | Fam | F | N | Y | A | ND | 82% | / | / | / | Exercise interolance, premature fatigue |  |
| 10 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-V4 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 11 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-V5 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 12 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-V6 | Fam | F | N | N | A | 7 | 52% | / | / | / | Healthy |  |
| 13 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-V7 | Fam | M | N | Y | D | 10 weeks | / | / | / | / | Sudden infant death |  |
| 14 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-V8 | Fam | F | Y | Y | D | 9 months | Homo | Homo | / | Homo (Heart) | Congestive heart failur, muscle hypotonia, lactic acidosis |  |
| 15 | 3303 | m.3303C\>T | C3303T\-F1 | C3303T\-F1\-V9 | Fam | M | N | Y | D | 3 months | Homo | Homo | / | Homo (Heart) | Congestive heart failur, lactic acidosis |  |
| 16 | 3303 | m.3303C\>T | C3303T\-F2 | C3303T\-F2\-I2 | Uninf | F | N | N | A | ND | 67% | / | / | / | Healthy |  |
| 17 | 3303 | m.3303C\>T | C3303T\-F2 | C3303T\-F2\-II1 | Fam | F | N | N | A | ND | 26% | / | / | / | Healthy |  |
| 18 | 3303 | m.3303C\>T | C3303T\-F2 | C3303T\-F2\-II2 | Fam | M | Y | Y | D | 6 months | / | Homo | / | Homo (Heart) | Cardiomyopathy |  |
| 19 | 3303 | m.3303C\>T | C3303T\-F2 | C3303T\-F2\-II3 | Fam | M | N | N | A | ND | 74% | / | / | / | Healthy |  |
| 20 | 3303 | m.3303C\>T | C3303T\-F3 | C3303T\-F3\-I2 | Uninf | F | N | N | A | ND | 67% | / | / | / | Healthy |  |
| 21 | 3303 | m.3303C\>T | C3303T\-F3 | C3303T\-F3\-II1 | Fam | F | N | N | A | ND | 26% | / | / | / | Healthy |  |
| 22 | 3303 | m.3303C\>T | C3303T\-F3 | C3303T\-F3\-II2 | Fam | M | Y | Y | D | 6 months | \>98% | \>98% | / | \>98% (Heart) | Infantile cardiomyopathy |  |
| 23 | 3303 | m.3303C\>T | C3303T\-F3 | C3303T\-F3\-II3 | Fam | F | N | N | A | ND | 74% | / | / | / | Healthy |  |
| 24 | 3303 | m.3303C\>T | C3303T\-F4 | C3303T\-F4\-I2 | Uninf | F | N | N | A | ND | 58% | / | / | / | Healthy |  |
| 25 | 3303 | m.3303C\>T | C3303T\-F4 | C3303T\-F4\-II1 | Fam | M | Y | Y | A | 3 | / | 97% | / | 92% (F) | Proximal limb and neck weakness, cardiac dysfunction |  |
| 26 | 3303 | m.3303C\>T | C3303T\-F4 | C3303T\-F4\-II2 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 27 | 3303 | m.3303C\>T | C3303T\-F4 | C3303T\-F4\-II3 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 28 | 3303 | m.3303C\>T | C3303T\-F5 | C3303T\-F5\-I2 | Uninf | F | N | Y | A | 25 | / | \>98% | / | / | Skeletal myopathy, cardiomyopathy |  |
| 29 | 3303 | m.3303C\>T | C3303T\-F5 | C3303T\-F5\-II1 | Fam | M | N | Y | A | 20 | / | \>98% | / | / | Skeletal myopathy |  |
| 30 | 3303 | m.3303C\>T | C3303T\-F5 | C3303T\-F5\-II2 | Fam | F | N | Y | A | 27 | / | \>98% | / | / | Skeletal myopathy |  |
| 31 | 3303 | m.3303C\>T | C3303T\-F5 | C3303T\-F5\-III1 | Fam | F | Y | Y | A | 16 | / | \>98% | / | / | Skeletal myopathy, cardiomyopathy |  |
| 32 | 3303 | m.3303C\>T | C3303T\-F6 | C3303T\-F6\-I2 | Uninf | F | N | N | A | 48 | / | / | / | / | Healthy |  |
| 33 | 3303 | m.3303C\>T | C3303T\-F6 | C3303T\-F6\-II1 | Fam | M | N | N | A | 28 | / | / | / | / | Healthy |  |
| 34 | 3303 | m.3303C\>T | C3303T\-F6 | C3303T\-F6\-II2 | Fam | F | N | N | A | 25 | / | / | / | / | Healthy |  |
| 35 | 3303 | m.3303C\>T | C3303T\-F6 | C3303T\-F6\-II3 | Fam | F | N | Y | D | 7 months | / | / | / | / | Cardiomyopathy |  |
| 36 | 3303 | m.3303C\>T | C3303T\-F6 | C3303T\-F6\-II4 | Fam | F | Y | Y | D | 3 months | / | 35% | / | \>98% (Heart) | Skeletal myopathy, cardiomyopathy |  |
| 37 | 3303 | m.3303C\>T | C3303T\-F7 | C3303T\-F7\-I1 | Uninf | F | N | Y | D | 60 | / | / | / | / | Early dementia |  |
| 38 | 3303 | m.3303C\>T | C3303T\-F7 | C3303T\-F7\-II1 | Fam | F | N | Y | D | 30 | / | / | / | / | Psychiatric illness characterized by psychoses and recurrent episodes of depression |  |
| 39 | 3303 | m.3303C\>T | C3303T\-F7 | C3303T\-F7\-III1 | Fam | F | N | Y | A | 33 | 25% | / | / | / | Short stature, migraine, early fatigue, psychiatric illness characterized by psychoses and recurrent episodes of depression |  |
| 40 | 3303 | m.3303C\>T | C3303T\-F7 | C3303T\-F7\-III2 | Fam | F | N | Y | A | 37 | 20% | / | / | / | Short stature, psychoses, maniac\-depressive crises |  |
| 41 | 3303 | m.3303C\>T | C3303T\-F7 | C3303T\-F7\-IV1 | Fam | F | Y | Y | A | 6 | 75% | 95% | / | / | Pneumonia, tachypnoea, lip cyanosis, cardiomegaly, left ventricular hypertrophy, delayed motor development, proximal weakness, lumbar lordosis, modified Gowers sign, easy fatigability, frequent falls, hyperlactatemia. |  |
| 42 | 3303 | m.3303C\>T | C3303T\-F7 | C3303T\-F7\-IV2 | Fam | F | N | N | A | 10 | 42% | / | / | / | Healthy |  |
| 43 | 3303 | m.3303C\>T | C3303T\-F7 | C3303T\-F7\-IV3 | Fam | F | N | N | A | 3 | 57% | / | / | / | Healthy |  |
| 44 | 3303 | m.3303C\>T | C3303T\-F8 | C3303T\-F8\-P1 | Uninf | M | Y | Y | A | 35 | 92% | 98% | 98% | 95% (F), 82% (BM), 98% (H) | Hypertrophic cardiomyopathy |  |
| 45 | 3303 | m.3303C\>T | C3303T\-F9 | C3303T\-F9\-P1 | Uninf | M | Y | Y | A | 2 | / | 97\.2% | / | / | Myopathy |  |
| 46 | 3303 | m.3303C\>T | C3303T\-F10 | C3303T\-F10\-P1 | Uninf | M | Y | Y | A | 6 | 36% | / | / | / | Myopathy |  |

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