G9804A

# **General Information**

| **Position** | **9804** | **Variant** | **m.9804G\>A** | **Locus** | **MT\-CO3** | **Amino\-AcidChange** | **A200T** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | VUS | **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.9804G\>A** variant in MT\-CO3 has been reported in 4 pedigrees. To date, 8 carriers have been reported. Homoplasmy was reported in 2/8 carriers (25%), and 4/8 carriers (50%) were affected. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in bone marrow (6\.9%) than in blood (2\.8%). In one unaffected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in blood (2\.7%) than in bone marrow (0\.1%). The main clinical manifestations among affected carriers included LHON, mS\-affected cotwin, tetralogy of Fallot, vEP abnormalities, visual impairment OU, atrophy, bilateral optic disc pallor, hypoxic spells, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 9804 | m.9804G\>A | [G9804A\-F1](https://mitofam.com/doc/1671/) | Turkey | LHON | 3 | 0 | 2001 | [11339587](https://pubmed.ncbi.nlm.nih.gov/11339587/) |  |
| 2 | 9804 | m.9804G\>A | G9804A\-F2 | Turkey | Tetralogy of Fallot with psychomotor/growth retardation | ND | ND | 2014 | [23735083](https://pubmed.ncbi.nlm.nih.gov/23735083/) |  |
| 3 | 9804 | m.9804G\>A | [G9804A\-F3](https://mitofam.com/doc/1672/) | Germany | multiple sclerosis context; candidate LHON\-related mutation | 1 | 0 | 2016 | [27119776](https://pubmed.ncbi.nlm.nih.gov/27119776/) |  |
| 4 | 9804 | m.9804G\>A | G9804A\-F4 | Switzerland | Inherited optic neuropathy; LHON\-like optic atrophy | ND | ND | 2019 | [30831606](https://pubmed.ncbi.nlm.nih.gov/30831606/) |  |

# **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 | 9804 | m.9804G\>A | G9804A\-F1 | G9804A\-F1\-II1 | Fam | ND | Y | Y | ND | ND | \+ | / | / | / | LHON; painless subacute bilateral optic neuropathy |  |
| 2 | 9804 | m.9804G\>A | G9804A\-F1 | G9804A\-F1\-II2 | Fam | F | N | N | ND | ND | \+ | / | / | / | Asymptomatic; no optic neuropathy |  |
| 3 | 9804 | m.9804G\>A | G9804A\-F1 | G9804A\-F1\-III1 | Fam | F | N | N | ND | ND | \+ | / | / | / | Asymptomatic; no optic neuropathy |  |
| 4 | 9804 | m.9804G\>A | G9804A\-F1 | G9804A\-F1\-III2 | Fam | M | N | N | ND | ND | \+ | / | / | / | Asymptomatic; no optic neuropathy |  |
| 5 | 9804 | m.9804G\>A | G9804A\-F2 | G9804A\-F2\-P1 | Uninf | M | Y | Y | A | 7mo | / | / | / | heart Homo | Tetralogy of Fallot; severe cyanosis/hypoxic spells; psychomotor and growth retardation |  |
| 6 | 9804 | m.9804G\>A | G9804A\-F3 | G9804A\-F3\-I1 | Uninf | ND | Y | Y | ND | ND | 2\.8% | / | / | 6\.9%(BM) | MS\-affected cotwin; no optic neuropathy reported |  |
| 7 | 9804 | m.9804G\>A | G9804A\-F3 | G9804A\-F3\-II1 | Uninf | ND | N | N | ND | ND | 2\.7% | / | / | 0\.1%(BM) | Nonaffected cotwin |  |
| 8 | 9804 | m.9804G\>A | G9804A\-F4 | G9804A\-F4\-I1 | Uninf | M | Y | Y | ND | 18 | Homo | / | / | / | Visual impairment OU, bilateral optic disc pallor/atrophy, paracentral scotomas, red\-green deficiency, VEP abnormalities |  |

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