A3260G

# **General Information**

| **Position** | **3260** | **Variant** | **m.3260A\>G** | **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.3260A\>G** variant in MT\-TL1 has been reported in 6 pedigrees. To date, 67 carriers have been reported. Reported mutation loads ranged from 4% to 90%, with a median of 47\.5% overall; affected carriers showed mutation loads from 4% to 90%, with a median of 60%; unaffected carriers showed mutation loads from 5% to 78%, with a median of 40%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (86%) than in blood (22%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (84%) than in blood (32%). Similar tissue\-specific differences were observed in 1 additional carriers. The main clinical manifestations among affected carriers included short stature, exercise intolerance, migraine, fatigue, cardiomyopathy, seizures, exertional dyspnoea, GERD, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3260 | m.3260A\>G | [A3260G\-F1](https://mitofam.com/doc/2236/) | Italy | Myopathy, cardiomyopathy | 15 | 4 | 1991 | [1677065](https://pubmed.ncbi.nlm.nih.gov/1677065/) |  |
| 2 | 3260 | m.3260A\>G | [A3260G\-F2](https://mitofam.com/doc/2237/) | UK | Myopathy, cardiomyopathy | 6 | 4 | 1993 | [8210299](https://pubmed.ncbi.nlm.nih.gov/8210299/) |  |
| 3 | 3260 | m.3260A\>G | [A3260G\-F3 ](https://mitofam.com/doc/2238/)| Japan | MELAS | 3 | 0 | 1996 | [8941275](https://pubmed.ncbi.nlm.nih.gov/8941275/) |  |
| 4 | 3260 | m.3260A\>G | [A3260G\-F4](https://mitofam.com/doc/2239/) | Italy | MELAS, cardiomyopathy, rhabdomyolysis, autism | 18 | 8 | 2010 | [20965148](https://pubmed.ncbi.nlm.nih.gov/20965148/) |  |
| 5 | 3260 | m.3260A\>G | [A3260G\-F5 ](https://mitofam.com/doc/2240/)| China | MELAS | 2 | 0 | 2014 | [24656211](https://pubmed.ncbi.nlm.nih.gov/24656211/) |  |
| 6 | 3260 | m.3260A\>G | A3260G\-F6 | USA | Hypertrophic cardiomyopathy, skeletal muscle myopathy, seizures, and lactic acidosis | ND | ND | 2008 | [19036942](https://pubmed.ncbi.nlm.nih.gov/19036942/) |  |

# **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 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-I2 | Uninf | F | N | N | D | ND | / | / | / | / | Healthy |  |
| 2 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-II2 | Fam | F | N | Y | A | 30 | / | 89% | / | / | Exercise intolerance |  |
| 3 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-II4 | Fam | F | N | N | A | 58 | / | 78% | / | / | Healthy |  |
| 4 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-II5 | Fam | F | N | N | A | 56 | / | 39% | / | / | Healthy |  |
| 5 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-II8 | Fam | M | N | N | A | 64 | / | 60% | / | / | Healthy |  |
| 6 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-II10 | Fam | M | N | N | D | ND | / | / | / | / | Healthy |  |
| 7 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-II12 | Fam | M | N | N | A | 52 | / | 63% | / | / | Healthy |  |
| 8 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III1 | Fam | M | Y | Y | A | 23 | / | 90% | / | / | Exertional dyspnoea, tachycardia, and general muscle weakness. Hypotrophy, enlarged liver, bilateral ankle oedema |  |
| 9 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III2 | Fam | F | N | Y | A | 20 | / | 87% | / | / | Exercise intolerance, exertional dyspnoea |  |
| 10 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III3 | Fam | M | N | N | A | 37 | / | 57% | / | / | Healthy |  |
| 11 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III4 | Fam | M | N | N | A | 33 | / | 59% | / | / | Healthy |  |
| 12 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III5 | Fam | F | N | Y | A | 29 | / | 86% | / | / | Fatigability, muscle pain, exertional dyspnoea |  |
| 13 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III6 | Fam | M | N | N | A | 19 | / | 47% | / | / | Healthy |  |
| 14 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III7 | Fam | F | N | N | A | 34 | / | 20% | / | / | Healthy |  |
| 15 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III8 | Fam | F | N | N | A | 27 | / | 22% | / | / | Healthy |  |
| 16 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III9 | Fam | M | N | Y | D | 30 | / | 87% | / | / | Diabetes mellitus, bilateral cataract, type\-A Wolff\-Parkinson\-White pre\-excitation syndrome |  |
| 17 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III10 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 18 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-III11 | Fam | M | N | N | A | 25 | / | 63% | / | / | Healthy |  |
| 19 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-IV2 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 20 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-IV5 | Fam | ND | N | N | A | ND | / | / | / | / | Healthy |  |
| 21 | 3260 | m.3260A\>G | A3260G\-F1 | A3260G\-F1\-IV6 | Fam | ND | N | N | A | ND | / | / | / | / | Healthy |  |
| 22 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-II5 | Uninf | F | N | Y | A | ND | / | / | / | / | Myopathy, cardiomyopathy |  |
| 23 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-III3 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 24 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-III5 | Fam | F | N | Y | A | ND | / | / | / | / | Tiredness, leg aching, absent leg reflexes |  |
| 25 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-III6 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 26 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-III7 | Fam | F | N | Y | D | ND | / | / | / | / | Weakness, leg pain, leg swelling, chest pain, abdominal pain, breathlessness, nausea, palpitations, unproductive cough, malaise, cardiac failure, hepatic enlargement, absent reflexes, cardiomegaly, hyperkinetic heart, pneumonia, renal failure |  |
| 27 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-III8 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 28 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-III9 | Fam | F | Y | Y | A | ND | / | / | / | / | Myopathy, cardiomyopathy |  |
| 29 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-III10 | Fam | F | N | N | A | ND | / | / | / | / | Fatigability, leg swelling, weakness, exercise intolerance, exercise\-induced weakness, calf and thigh aching, generalized muscle weakness, mild bilateral ptosis, depressed reflexes, aortic systolic ejection murmur, malaise |  |
| 30 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-IV3 | Fam | M | N | Y | A | ND | / | / | / | / | Lethargy, leg giving way, aortic systolic murmur |  |
| 31 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-IV4 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 32 | 3260 | m.3260A\>G | A3260G\-F2 | A3260G\-F2\-IV5 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 33 | 3260 | m.3260A\>G | A3260G\-F3 | A3260G\-F3\-I2 | Uninf | F | N | N | A | ND | 29\.4% | / | / | / | Healthy |  |
| 34 | 3260 | m.3260A\>G | A3260G\-F3 | A3260G\-F3\-II1 | Fam | M | N | N | A | ND | 31\.6% | / | / | / | Healthy |  |
| 35 | 3260 | m.3260A\>G | A3260G\-F3 | A3260G\-F3\-II2 | Fam | M | N | N | A | ND | 44\.1% | / | / | / | Healthy |  |
| 36 | 3260 | m.3260A\>G | A3260G\-F3 | A3260G\-F3\-II3 | Fam | F | Y | Y | A | 6 | 87\.1% | / | / | / | MELAS |  |
| 37 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-I1 | Uninf | F | N | Y | D | ND | / | / | / | / | Migraine, short stature |  |
| 38 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-II1 | Fam | F | N | Y | D | ND | / | / | / | / | Migraine, short stature |  |
| 39 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-III1 | Fam | F | N | Y | D | ND | / | / | / | / | Migraine |  |
| 40 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-III2 | Fam | M | N | Y | D | ND | / | / | / | / | MELAS, cardiomyopathy, rhabdomyolysis, autism |  |
| 41 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-III3 | Fam | F | N | Y | A | ND | / | / | / | / | Migraine, short stature |  |
| 42 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV1 | Fam | M | N | Y | A | ND | / | / | / | / | Migraine, short stature |  |
| 43 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV2 | Fam | F | N | Y | D | 47 | 22% | 86% | / | / | Stroke, fatigue, exercise intolerance, seizures,constipation/GERD, migraine, short stature |  |
| 44 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV3 | Fam | M | N | Y | A | 46 | / | / | / | / | Simple headache, short stature |  |
| 45 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV4 | Fam | M | N | Y | A | 45 | 32% | 84% | / | / | Exercise intolerance, migraine, short stature |  |
| 46 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV5 | Fam | F | N | Y | A | 45 | 11% | 81% | / | / | Stroke, fatigue, exercise intolerance, constipation/GERD, migraine, short stature |  |
| 47 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV6 | Fam | F | N | N | A | 43 | / | 40% | / | / | Simple headache, short stature |  |
| 48 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV7 | Fam | F | N | N | A | 42 | \<5% | / | / | / | Simple headache |  |
| 49 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV8 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 50 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV9 | Fam | F | N | Y | A | 41 | 15% | / | / | / | Neuropathy, migraine, short stature |  |
| 51 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-IV10 | Fam | F | N | Y | A | 32 | 27% | / | / | / | Exercise intolerance, neuropathy, short stature |  |
| 52 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V1 | Fam | F | N | Y | A | 21 | 55% | / | / | / | fatigue, exercise intolerance, simple headache, short stature |  |
| 53 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V2 | Fam | F | Y | Y | A | 20 | 48% | / | / | / | Stroke, fatigue, exercise intolerance, seizures, cardiomyopathy, neuropathy, migraine, short stature |  |
| 54 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V3 | Fam | F | N | Y | A | 17 | 60% | / | / | / | Fatigue, exercise intolerance, seizures, constipation/GERD, migraine, short stature |  |
| 55 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V4 | Fam | M | N | Y | A | 17 | \<5% | / | / | / | Exercise intolerance, short stature |  |
| 56 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V5 | Fam | F | N | Y | A | 14 | 17% | / | / | / | Exercise intolerance, simple headache. short stature |  |
| 57 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V6 | Fam | F | N | N | A | 9 | / | / | / | / | Healthy |  |
| 58 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V7 | Fam | M | N | N | A | ND | / | / | / | / | Simple headache |  |
| 59 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V8 | Fam | M | N | N | A | ND | / | / | / | / | Simple headache |  |
| 60 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V9 | Fam | M | N | N | A | 10 | / | / | / | / | Healthy |  |
| 61 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V10 | Fam | F | N | N | A | 7 | / | / | / | / | Healthy |  |
| 62 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V11 | Fam | M | N | Y | A | 5 | 4% | / | / | / | Autism |  |
| 63 | 3260 | m.3260A\>G | A3260G\-F4 | A3260G\-F4\-V12 | Fam | M | N | Y | A | 4 | 18% | / | / | / | Autism |  |
| 64 | 3260 | m.3260A\>G | A3260G\-F5 | A3260G\-F5\-I2 | Uninf | F | N | N | A | ND | 5% | / | / | / | Healthy |  |
| 65 | 3260 | m.3260A\>G | A3260G\-F5 | A3260G\-F5\-II1 | Fam | F | Y | Y | A | ND | / | 85% | / | / | MELAS |  |
| 66 | 3260 | m.3260A\>G | A3260G\-F5 | A3260G\-F5\-II2 | Fam | F | N | N | A | ND | / | 38% | / | / | Healthy |  |
| 67 | 3260 | m.3260A\>G | A3260G\-F6 | A3260G\-F6\-P1 | Uninf | ND | Y | Y | A | 13 | / | / | / | 80% (F) | Hypertrophic cardiomyopathy, skeletal muscle myopathy, seizures, and lactic acidosis |  |

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