A4295G

# **General Information**

| **Position** | **4295** | **Variant** | **m.4295A\>G** | **Locus** | **MT\-TI** | **RNA** | **tRNA Ile** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **mitoTIP** | 44\.00% | **Pathogenicity** | Reported \[VUS] |

"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.4295A\>G** variant in MT\-TI has been reported in 5 pedigrees. To date, 40 carriers have been reported. Homoplasmy was reported in 28/40 carriers (70%), and 22/40 carriers (55%) were affected. In one unaffected carrier, the mutation was undetectable in blood (0%) but exceeded 20% in hair (46\.1%). In one unaffected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in hair (34\.1%) than in blood (11\.7%). Similar tissue\-specific differences were observed in 5 additional carriers. The main clinical manifestations among affected carriers included maternally inherited deafness, hypertension, nonsyndromic hearing loss, hypertrophic cardiomyopathy, dilated Cardiomyopathy, and deafness.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 4295 | m.4295A\>G | [A4295G\-F1](https://mitofam.com/doc/604/) | Canada | Hypertrophic cardiomyopathy | 11 | 1 | 1996 | [8889580](https://pubmed.ncbi.nlm.nih.gov/8889580/) |  |
| 2 | 4295 | m.4295A\>G |[ A4295G\-F2](https://mitofam.com/doc/605/) | China | Hypertension | 0 | 4 | 2008 | [18177739](https://pubmed.ncbi.nlm.nih.gov/18177739/) |  |
| 3 | 4295 | m.4295A\>G | [A4295G\-F3](https://mitofam.com/doc/606/) | France | Nonsyndromic hearing loss | 2 | 4 | 2012 | [22241583](https://pubmed.ncbi.nlm.nih.gov/22241583/) |  |
| 4 | 4295 | m.4295A\>G | [A4295G\-F4](https://mitofam.com/doc/607/) | China | Maternally inherited deafness | 5 | 8 | 2021 | [33398350](https://pubmed.ncbi.nlm.nih.gov/33398350/) |  |
| 5 | 4295 | m.4295A\>G | A4295G\-F5 | China | Dilated Cardiomyopathy,Deafness, hypertension | NA | NA | 2022 | [34991096](https://pubmed.ncbi.nlm.nih.gov/34991096/) |  |

# **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 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-I2 | Uninf | F | N | N | A | ND | 8\.7% | / | / | / | Healthy |  |
| 2 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-II1 | Fam | M | N | N | A | ND | 0 | / | / | 46\.1%(H) | Healthy |  |
| 3 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-II2 | Fam | M | N | N | A | ND | 37\.8% | / | / | 46%(H) | Healthy |  |
| 4 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-II3 | Fam | M | N | N | A | ND | 11\.7% | / | / | 34\.1%(H) | Healthy |  |
| 5 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-II4 | Fam | M | N | N | A | ND | 44\.6% | / | / | 0%(H) | Healthy |  |
| 6 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-II5 | Fam | F | N | N | A | ND | 0 | / | / | Homo(H) | Healthy |  |
| 7 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-II6 | Fam | F | N | N | A | ND | / | / | / | 58\.0%(H) | Healthy |  |
| 8 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-II7 | Fam | F | N | N | A | ND | / | / | / | 81%(H) | Healthy |  |
| 9 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-II8 | Fam | F | N | N | A | 32 | 26\.7% | / | / | 78\.2%(H) | Healthy |  |
| 10 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-III1 | Fam | F | Y | Y | D | 7 months | / | / | / | 90\.4%(heart);81\.2%(liver) | Hypertrophic cardiomyopathy |  |
| 11 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-III2 | Fam | M | N | Y | A | 5 | 47\.7% | / | / | 89\.5%(heart);100%(H) | Hypertrophic cardiomyopathy |  |
| 12 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-III3 | Fam | M | N | N | A | 6 | 26\.2% | / | / | 15%(H) | Healthy |  |
| 13 | 4295 | m.4295A\>G | A4295G\-F1 | A4295G\-F1\-III4 | Fam | F | N | N | A | 2 | 19\.5% | / | / | 7\.4%(H) | Healthy |  |
| 14 | 4295 | m.4295A\>G | A4295G\-F2 | A4295G\-F2\-I2 | Uninf | F | N | Y | A | ND | Homo | / | / | / | Hypertension |  |
| 15 | 4295 | m.4295A\>G | A4295G\-F2 | A4295G\-F2\-II1 | Fam | M | Y | Y | A | 51 | Homo | / | / | / | Hypertension |  |
| 16 | 4295 | m.4295A\>G | A4295G\-F2 | A4295G\-F2\-II2 | Fam | F | N | Y | A | ND | Homo | / | / | / | Hypertension |  |
| 17 | 4295 | m.4295A\>G | A4295G\-F2 | A4295G\-F2\-III1 | Fam | F | N | Y | A | ND | Homo | / | / | / | Hypertension |  |
| 18 | 4295 | m.4295A\>G | A4295G\-F2 | A4295G\-F2\-III2 | Fam | M | N | Y | A | ND | Homo | / | / | / | Hypertension |  |
| 19 | 4295 | m.4295A\>G | A4295G\-F3 | A4295G\-F3\-I2 | Uninf | F | N | Y | D | ND | Homo | / | / | / | Nonsyndromic hearing loss |  |
| 20 | 4295 | m.4295A\>G | A4295G\-F3 | A4295G\-F3\-II2 | Fam | F | N | Y | A | ND | Homo | / | / | / | Nonsyndromic hearing loss |  |
| 21 | 4295 | m.4295A\>G | A4295G\-F3 | A4295G\-F3\-III1 | Fam | F | N | Y | A | ND | Homo | / | / | / | Nonsyndromic hearing loss |  |
| 22 | 4295 | m.4295A\>G | A4295G\-F3 | A4295G\-F3\-III2 | Fam | F | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 23 | 4295 | m.4295A\>G | A4295G\-F3 | A4295G\-F3\-III3 | Fam | F | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 24 | 4295 | m.4295A\>G | A4295G\-F3 | A4295G\-F3\-III4 | Fam | F | Y | Y | A | ND | Homo | / | / | / | Nonsyndromic hearing loss |  |
| 25 | 4295 | m.4295A\>G | A4295G\-F3 | A4295G\-F3\-III5 | Fam | F | N | Y | A | ND | Homo | / | / | / | Nonsyndromic hearing loss |  |
| 26 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-I2 | Uninf | F | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 27 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-II2 | Fam | F | N | Y | A | 61 | Homo | / | / | / | Maternally inherited deafness |  |
| 28 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-II4 | Fam | F | N | N | A | 58 | Homo | / | / | / | Healthy |  |
| 29 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-II6 | Fam | F | N | Y | A | 55 | Homo | / | / | / | Maternally inherited deafness |  |
| 30 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-II7 | Fam | M | N | Y | A | 53 | Homo | / | / | / | Maternally inherited deafness |  |
| 31 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-II9 | Fam | M | N | Y | A | 50 | Homo | / | / | / | Maternally inherited deafness |  |
| 32 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-III1 | Fam | M | N | Y | A | 33 | Homo | / | / | / | Maternally inherited deafness |  |
| 33 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-III2 | Fam | F | N | Y | A | 28 | Homo | / | / | / | Maternally inherited deafness |  |
| 34 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-III3 | Fam | M | N | Y | A | 29 | Homo | / | / | / | Maternally inherited deafness |  |
| 35 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-III4 | Fam | M | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 36 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-III5 | Fam | F | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 37 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-III6 | Fam | F | N | Y | A | 27 | Homo | / | / | / | Maternally inherited deafness |  |
| 38 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-III7 | Fam | F | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 39 | 4295 | m.4295A\>G | A4295G\-F4 | A4295G\-F4\-III8 | Fam | M | Y | Y | A | 24 | Homo | / | / | / | Maternally inherited deafness |  |
| 40 | 4295 | m.4295A\>G | A4295G\-F5 | A4295G\-F5\-P1 | Uninf | F | Y | Y | A | 60 | Homo | / | / | / | Dilated Cardiomyopathy,deafness, hypertension |  |

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