A3395G

# General Information

| **Position** | **3395** | **Variant** | **m.3395A\>G** | **Locus** | **MT\-ND1** | **Amino\-AcidChange** | **Y30C** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | VUS\+ | **Pathogenicity** | Reported |

"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.3395A\>G** variant in MT\-ND1 has been reported in 5 pedigrees. To date, 13 carriers have been reported. Homoplasmy was reported in 8/13 carriers (61\.5%), and 8/13 carriers (61\.5%) were affected. The main clinical manifestations among affected carriers included exercise intolerance, cerebellar ataxia, deafness, hypertrophic cardiomyopathy and severe sensorineural hearing loss, lHON with epilepsy and mild cognitive features, postlingual hearing loss, profound hearing impairment, progressive deafness, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3395 | m.3395A\>G | A3395G\-F1 | Tunisia | Hypertrophic cardiomyopathy / sensorineural hearing loss | 3 | 0 | 2011 | [21144833](https://pubmed.ncbi.nlm.nih.gov/21144833/) | Carrying m.4316A\>G. |
| 2 | 3395 | m.3395A\>G | [A3395G\-F2 ](https://mitofam.com/doc/1391/)| Denmark/Greenland | LHON | 2 | 0 | 2017 | [28139165](https://pubmed.ncbi.nlm.nih.gov/28139165/) |  |
| 3 | 3395 | m.3395A\>G | A3395G\-F3 | France | Profound hearing impairment | 0 | 0 | 2020 | [32011699](https://pubmed.ncbi.nlm.nih.gov/32011699/) |  |
| 4 | 3395 | m.3395A\>G |[ A3395G\-F4](https://mitofam.com/doc/1392/) | France | Hearing loss / exercise intolerance | 0 | 3 | 2020 | [32011699](https://pubmed.ncbi.nlm.nih.gov/32011699/) |  |
| 5 | 3395 | m.3395A\>G | A3395G\-F5 | France | Cerebellar ataxia / cerebellar syndrome | 0 | 0 | 2020 | [32011699](https://pubmed.ncbi.nlm.nih.gov/32011699/) |  |

# 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 | 3395 | m.3395A\>G | A3395G\-F1 | A3395G\-F1\-I2 | Uninf | F | N | N | A | ND | 58% | / | / | / | Healthy |  |
| 2 | 3395 | m.3395A\>G | A3395G\-F1 | A3395G\-F1\-II1 | Fam | F | Y | Y | A | 1 | 98% | / | / | / | Hypertrophic cardiomyopathy and severe sensorineural hearing loss |  |
| 3 | 3395 | m.3395A\>G | A3395G\-F1 | A3395G\-F1\-II2 | Fam | F | N | N | A | ND | 68% | / | / | / | Healthy |  |
| 4 | 3395 | m.3395A\>G | A3395G\-F1 | A3395G\-F1\-II3 | Fam | F | N | N | A | ND | 68\.5% | / | / | / | Healthy |  |
| 5 | 3395 | m.3395A\>G | A3395G\-F2 | A3395G\-F2\-I1 | Uninf | F | N | N | A | 51 | Homo | / | / | / | No visual disorder |  |
| 6 | 3395 | m.3395A\>G | A3395G\-F2 | A3395G\-F2\-II1 | Fam | F | Y | Y | A | 30 | Homo | Homo | / | / | LHON with epilepsy and mild cognitive features |  |
| 7 | 3395 | m.3395A\>G | A3395G\-F2 | A3395G\-F2\-II2 | Fam | F | N | N | A | 24 | Homo | / | / | / | No visual disorder |  |
| 8 | 3395 | m.3395A\>G | A3395G\-F3 | A3395G\-F3\-I1 | De novo | M | Y | Y | A | 3 | 52% | / | / | / | Profound hearing impairment | Mother tested negative for m.3395A\>G; no family history. |
| 9 | 3395 | m.3395A\>G | A3395G\-F4 | A3395G\-F4\-I1 | Uninf | F | N | Y | A | 35 | Homo | / | / | / | Sudden left profound deafness with tinnitus | Mutation found in mother of family 2 patients; age is age at deafness because examination age is not reported. |
| 10 | 3395 | m.3395A\>G | A3395G\-F4 | A3395G\-F4\-II1 | Fam | F | Y | Y | A | 25 | Homo | / | / | / | Postlingual hearing loss | No arrowed proband; first listed patient used as index. |
| 11 | 3395 | m.3395A\>G | A3395G\-F4 | A3395G\-F4\-II2 | Fam | F | N | Y | A | 32 | Homo | / | / | / | Progressive deafness, exercise intolerance, megacolon, hypertension |  |
| 12 | 3395 | m.3395A\>G | A3395G\-F4 | A3395G\-F4\-II3 | Fam | M | N | Y | A | 18 | Homo | / | / | / | Deafness, exercise intolerance, pes cavus | Family\-level homoplasmy; cybrid made from P2c platelets. |
| 13 | 3395 | m.3395A\>G | A3395G\-F5 | A3395G\-F5\-I1 | De novo | F | Y | Y | A | 51 | Homo | / | / | / | Cerebellar ataxia / cerebellar syndrome | Mother tested negative; no siblings and no family history. |

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