C4640A

# **General Information**

| **Position** | **4640** | **Variant** | **m.4640C\>A** | **Locus** | **MT\-ND2** | **Amino\-AcidChange** | **I57M** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \- | **APOGEE2** | Likely\-benign | **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.4640C\>A** variant in MT\-ND2 has been reported in 3 pedigrees. To date, 3 carriers have been reported. Homoplasmy was reported in 3/3 carriers (100%), and 3/3 carriers (100%) were affected. The main clinical manifestations among affected carriers included childhood sporadic bilateral optic neuropathy, lHON visual loss with recovery and later worsening, lHON\-associated visual loss after Wada test, pharmacoresistant temporal lobe epilepsy, insulin\-dependent diabetes, large cecocentral scotomas OU, and severe optic nerve hypoplasia OS.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 4640 | m.4640C\>A | C4640A\-F1 | Russia | LHON | 35 | 4 | 2001 | [11479733](https://pubmed.ncbi.nlm.nih.gov/11479733/) |  |
| 2 | 4640 | m.4640C\>A | C4640A\-F2 | Saudi Arabia | Sporadic bilateral optic neuropathy | ND | ND | 2008 | [18676632](https://pubmed.ncbi.nlm.nih.gov/18676632/) |  |
| 3 | 4640 | m.4640C\>A | C4640A\-F3 | Germany | Temporal lobe epilepsy and LHON\-associated visual loss | ND | ND | 2011 | [21145289](https://pubmed.ncbi.nlm.nih.gov/21145289/) |  |

# **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 | 4640 | m.4640C\>A | C4640A\-F1 | C4640A\-F1\-P1 | Uninf | ND | Y | Y | ND | 14y | Homo | / | / | / | LHON visual loss with recovery and later worsening |  |
| 2 | 4640 | m.4640C\>A | C4640A\-F2 | C4640A\-F2\-P1 | Uninf | M | Y | Y | A | 14y | Homo | / | / | / | Childhood sporadic bilateral optic neuropathy, severe optic nerve hypoplasia OS, large cecocentral scotomas OU |  |
| 3 | 4640 | m.4640C\>A | C4640A\-F3 | C4640A\-F3\-P1 | Uninf | M | Y | Y | A | 31y | Homo | Homo | / | Homo(brain) | Pharmacoresistant temporal lobe epilepsy, LHON\-associated visual loss after Wada test, insulin\-dependent diabetes |  |

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