G11696A

# **General Information**

| **Position** | **11696** | **Variant** | **m.11696G\>A** | **Locus** | **MT\-ND4** | **Amino\-AcidChange** | **V313I** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | VUS\- | **Pathogenicity** | Reported / possibly synergistic |

"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.11696G\>A** variant in MT\-ND4 has been reported in 17 pedigrees. To date, 40 carriers have been reported. Homoplasmy was reported in 32/40 carriers (80%), and 35/40 carriers (87\.5%) were affected. The main clinical manifestations among affected carriers included LHON, sensorineural hearing loss, visual acuity R, severe, 0\.1, lHON plus bilateral neurological symptoms, moderate, L 0\.1, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 11696 | m.11696G\>A | [G11696A\-F1](https://mitofam.com/doc/1885) | Netherlands | LHON; dystonia | 4 | 9 | 1996 | [8644732](https://pubmed.ncbi.nlm.nih.gov/8644732/) | Coexisting variant: Coexisting homoplasmic m.14596T\>A (ND6\) |
| 2 | 11696 | m.11696G\>A | G11696A\-F2 | China | LHON | 32 | 0 | 2006 | [16364244](https://pubmed.ncbi.nlm.nih.gov/16364244/) |  |
| 3 | 11696 | m.11696G\>A | G11696A\-F3 | China | LHON | 20 | 0 | 2006 | [16364244](https://pubmed.ncbi.nlm.nih.gov/16364244/) |  |
| 4 | 11696 | m.11696G\>A | G11696A\-F4 | China | LHON | 4 | 0 | 2006 | [16364244](https://pubmed.ncbi.nlm.nih.gov/16364244/) |  |
| 5 | 11696 | m.11696G\>A | G11696A\-F5 | China | LHON | 5 | 0 | 2006 | [16364244](https://pubmed.ncbi.nlm.nih.gov/16364244/) | Coexisting variant: coexisting A13549G |
| 6 | 11696 | m.11696G\>A | G11696A\-F6 | China | LHON | 7 | 0 | 2006 | [16364244](https://pubmed.ncbi.nlm.nih.gov/16364244/) |  |
| 7 | 11696 | m.11696G\>A |[ G11696A\-F7](https://mitofam.com/doc/1886/) | China | Aminoglycoside\-induced and nonsyndromic hearing loss | 9 | 9 | 2007 | [17723226](https://pubmed.ncbi.nlm.nih.gov/17723226/) | Coexisting variant: coexisting A1555G |
| 8 | 11696 | m.11696G\>A | G11696A\-F8 | China | LHON | 8 | 0 | 2011 | [21482521](https://pubmed.ncbi.nlm.nih.gov/21482521/) | Coexisting variant: coexisting T12338C |
| 9 | 11696 | m.11696G\>A | G11696A\-F9 | China | LHON | 14 | 0 | 2011 | [21482521](https://pubmed.ncbi.nlm.nih.gov/21482521/) | Coexisting variant: coexisting T12338C |
| 10 | 11696 | m.11696G\>A | G11696A\-F10 | China | LHON | 2 | 1 | 2016 | [27159682](https://pubmed.ncbi.nlm.nih.gov/27159682/) | Coexisting variant: coexisting G11778A |
| 11 | 11696 | m.11696G\>A | G11696A\-F11 | China | LHON | 7 | 3 | 2016 | [27159682](https://pubmed.ncbi.nlm.nih.gov/27159682/) | Coexisting variant: coexisting G11778A |
| 12 | 11696 | m.11696G\>A | G11696A\-F12 | China | LHON | 7 | 3 | 2016 | [27159682](https://pubmed.ncbi.nlm.nih.gov/27159682/) | Coexisting variant: coexisting G11778A |
| 13 | 11696 | m.11696G\>A | G11696A\-F13 | China | LHON | 9 | 2 | 2016 | [27159682](https://pubmed.ncbi.nlm.nih.gov/27159682/) | Coexisting variant: coexisting G11778A |
| 14 | 11696 | m.11696G\>A | G11696A\-F14 | China | LHON | 7 | 2 | 2016 | [27159682](https://pubmed.ncbi.nlm.nih.gov/27159682/) | Coexisting variant: coexisting G11778A |
| 15 | 11696 | m.11696G\>A | G11696A\-F15 | China | LHON | 3 | 8 | 2016 | [27159682](https://pubmed.ncbi.nlm.nih.gov/27159682/) | Coexisting variant: coexisting G11778A |
| 16 | 11696 | m.11696G\>A | G11696A\-F16 | China | LHON | 8 | 8 | 2016 | [27159682](https://pubmed.ncbi.nlm.nih.gov/27159682/) | Coexisting variant: coexisting G11778A |
| 17 | 11696 | m.11696G\>A | G11696A\-F17 | China | LHON | 5 | 2 | 2016 | [27159682](https://pubmed.ncbi.nlm.nih.gov/27159682/) | Coexisting variant: coexisting G11778A |

# **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 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-V1 | Fam | M | N | Y | A | ND | 89% | / | / | / | Neurological symptoms | Coexisting variant: Coexisting mutation\-load note: 11% wild\-type in blood. Additional homoplasmic variant: T14596A |
| 2 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-V2 | Fam | M | N | Y | A | ND | Homo | / | / | / | LHON plus bilateral neurological symptoms | Coexisting variant: Coexisting mutation\-load note: 0% wild\-type in blood. Additional homoplasmic variant: T14596A |
| 3 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VI1 | Fam | M | N | Y | A | ND | Homo | / | / | / | LHON plus unilateral neurological symptoms | Coexisting variant: Coexisting mutation\-load note: 0% wild\-type in blood |
| 4 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VI2 | Fam | F | N | N | A | ND | 85% | / | / | / | Healthy | Coexisting variant: Coexisting mutation\-load note: 15% wild\-type in blood. Additional homoplasmic variant: T14596A |
| 5 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VI3 | Fam | M | Y | Y | A | ND | Homo | / | / | / | LHON plus bilateral neurological symptoms; muscle complex I deficiency | Coexisting variant: homoplasmic T14596A |
| 6 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VI4 | Fam | M | N | N | A | ND | 89% | / | / | / | Healthy | Coexisting variant: Coexisting mutation\-load note: 11% wild\-type in blood. Additional homoplasmic variant: T14596A |
| 7 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VI5 | Fam | M | N | Y | A | ND | 77% | / | / | / | Neurological symptoms | Coexisting variant: Coexisting mutation\-load note: 23% wild\-type in blood. Additional homoplasmic variant: T14596A |
| 8 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VI6 | Fam | M | N | Y | D | ND | / | / | / | Homo(F); 88%(optic nerve) | LHON plus bilateral neurological symptoms; died age 59 | Coexisting variant: Coexisting mutation\-load note: No blood available |
| 9 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VI7 | Fam | M | N | Y | A | ND | 88% | / | / | / | LHON plus bilateral neurological symptoms | Coexisting variant: Coexisting mutation\-load note: 12% wild\-type in blood. Additional homoplasmic variant: T14596A |
| 10 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VI8 | Fam | M | N | Y | A | ND | Homo | / | / | / | LHON plus neurological symptoms | Coexisting variant: Coexisting mutation\-load note: 0% wild\-type in blood. Additional homoplasmic variant: T14596A |
| 11 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VI9 | Fam | F | N | N | A | ND | 86% | / | / | / | Healthy | Coexisting variant: Coexisting mutation\-load note: 14% wild\-type in blood. Additional homoplasmic variant: T14596A |
| 12 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VII1 | Fam | F | N | Y | A | ND | Homo | / | / | / | LHON | Coexisting variant: Coexisting mutation\-load note: 0% wild\-type in blood. Additional homoplasmic variant: T14596A |
| 13 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VII2 | Fam | F | N | Y | A | ND | 87% | / | / | / | LHON | Coexisting variant: Coexisting mutation\-load note: 13% wild\-type in blood |
| 14 | 11696 | m.11696G\>A | G11696A\-F1 | G11696A\-F1\-VII3 | Fam | M | N | N | A | ND | / | / | / | / | Healthy | Coexisting variant: Coexisting homoplasmic m.14596T\>A (ND6\) |
| 15 | 11696 | m.11696G\>A | G11696A\-F2 | G11696A\-F2\-IV11 | Fam | M | Y | Y | A | 17 | Homo | / | / | / | LHON; VA 0\.05 OD and 0\.03 OS; large centrocecal scotomas | Original carrier identifier: WZ7\-IV\-11 |
| 16 | 11696 | m.11696G\>A | G11696A\-F3 | G11696A\-F3\-IV2 | Fam | F | Y | Y | A | 15 | Homo | / | / | / | LHON; onset at age 14; tinnitus; VA 0\.05 OD and 0\.1 OS | Original carrier identifier: WZ8\-IV\-2 |
| 17 | 11696 | m.11696G\>A | G11696A\-F4 | G11696A\-F4\-III3 | Fam | F | Y | Y | A | 19 | Homo | / | / | / | LHON; onset at age 18; VA 0\.1 OD and 0\.08 OS | Original carrier identifier: WZ9\-III\-3 |
| 18 | 11696 | m.11696G\>A | G11696A\-F5 | G11696A\-F5\-III1 | Fam | F | Y | Y | A | 8 | Homo | / | / | / | LHON; onset at age 7; VA 0\.12 OD and 0\.4 OS | Original carrier identifier: WZ10\-III\-1; Coexisting variants: A13549G, G5820A |
| 19 | 11696 | m.11696G\>A | G11696A\-F6 | G11696A\-F6\-II2 | Fam | F | Y | Y | A | 38 | Homo | / | / | / | LHON; VA 0\.1 OU | Original carrier identifier: WZ11\-II\-2 |
| 20 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-II1 | Fam | F | N | Y | ND | ND | Homo | / | / | / | Sensorineural hearing loss; severe | Coexisting variant: A1555G |
| 21 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-II2 | Fam | M | N | Y | ND | ND | Homo | / | / | / | Sensorineural hearing loss; severe | Coexisting variant: A1555G |
| 22 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-III1 | Fam | F | N | Y | ND | ND | Homo | / | / | / | Sensorineural hearing loss; moderate | Coexisting variant: A1555G |
| 23 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-III2 | Fam | F | N | Y | ND | ND | Homo | / | / | / | Sensorineural hearing loss; moderate | Coexisting variant: A1555G |
| 24 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-III3 | Fam | M | N | Y | ND | ND | Homo | / | / | / | Sensorineural hearing loss; mild | Coexisting variant: A1555G |
| 25 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-III4 | Fam | F | N | Y | ND | ND | Homo | / | / | / | Sensorineural hearing loss; severe | Coexisting variant: A1555G |
| 26 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-III5 | Fam | M | N | Y | ND | ND | Homo | / | / | / | Sensorineural hearing loss; severe | Coexisting variant: A1555G |
| 27 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-III6 | Fam | F | N | Y | ND | ND | Homo | / | / | / | Sensorineural hearing loss; moderate | Coexisting variant: A1555G |
| 28 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-IV1 | Fam | F | Y | Y | ND | 17 | Homo | / | / | / | Aminoglycoside\-induced sensorineural hearing loss; moderate | Coexisting variant: A1555G |
| 29 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-IV2 | Fam | F | N | Y | ND | ND | Homo | / | / | / | Aminoglycoside\-induced sensorineural hearing loss; severe | Coexisting variant: A1555G |
| 30 | 11696 | m.11696G\>A | G11696A\-F7 | G11696A\-F7\-III7 | Fam | M | N | N | ND | ND | Homo | / | / | / | Healthy | Coexisting variant: A1555G |
| 31 | 11696 | m.11696G\>A | G11696A\-F8 | G11696A\-F8\-III1 | Fam | M | Y | Y | A | 17 years | Homo | / | / | / | LHON; bilateral visual loss since age 6; VA R 0\.06 L 0\.05; VEP P100 delayed |  |
| 32 | 11696 | m.11696G\>A | G11696A\-F9 | G11696A\-F9\-III4 | Fam | M | Y | Y | A | 20 years | Homo | / | / | / | LHON; poor vision since childhood; VA R 0\.1 L 0\.06; visual\-field constriction and central scotoma |  |
| 33 | 11696 | m.11696G\>A | G11696A\-F10 | G11696A\-F10\-II4 | Fam | M | Y | Y | A | 21 | Homo | / | / | / | LHON; Mild visual impairment; onset 21 years; visual acuity R/L 0\.1/0\.1 |  |
| 34 | 11696 | m.11696G\>A | G11696A\-F11 | G11696A\-F11\-IV2 | Fam | M | Y | Y | A | 18 | Homo | / | / | / | LHON; Moderate visual impairment; onset 18 years; visual acuity R/L 0\.08/0\.1 |  |
| 35 | 11696 | m.11696G\>A | G11696A\-F12 | G11696A\-F12\-III2 | Fam | M | Y | Y | A | 20 | Homo | / | / | / | LHON; Severe visual impairment; onset 19 years; visual acuity R/L 0\.05/0\.03 |  |
| 36 | 11696 | m.11696G\>A | G11696A\-F13 | G11696A\-F13\-III6 | Fam | M | Y | Y | A | 18 | Homo | / | / | / | LHON; Mild visual impairment; onset 15 years; visual acuity R/L 0\.1/0\.1 |  |
| 37 | 11696 | m.11696G\>A | G11696A\-F14 | G11696A\-F14\-III1 | Fam | M | Y | Y | A | 12 | Homo | / | / | / | LHON; Mild visual impairment; onset 12 years; visual acuity R/L 0\.12/0\.12 |  |
| 38 | 11696 | m.11696G\>A | G11696A\-F15 | G11696A\-F15\-III1 | Fam | M | Y | Y | A | 25 | Homo | / | / | / | LHON; Moderate visual impairment; onset 25 years; visual acuity R/L 0\.06/0\.1 |  |
| 39 | 11696 | m.11696G\>A | G11696A\-F16 | G11696A\-F16\-III10 | Fam | M | Y | Y | A | 35 | Homo | / | / | / | LHON; Profound visual impairment; onset 14 years; visual acuity R/L 0\.01/0\.05 |  |
| 40 | 11696 | m.11696G\>A | G11696A\-F17 | G11696A\-F17\-II8 | Fam | M | Y | Y | A | 10 | Homo | / | / | / | LHON; Severe visual impairment; onset 10 years; visual acuity R/L 0\.1/0\.05 |  |

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