G3460A

# General Information

| **Position** | **3460** | **Variant** | **m.3460G\>A** | **Locus** | **MT\-ND1** | **Amino\-AcidChange** | **A52T** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | Likely\-pathogenic | **Pathogenicity** | Cfrm \[P] |

"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.3460G\>A** variant in MT\-ND1 has been reported in 22 pedigrees. To date, 62 carriers have been reported. Homoplasmy was reported in 42/62 carriers (67\.7%), and 43/62 carriers (69\.4%) were affected. In one unaffected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in blood (56%) than in urine (24%). The main clinical manifestations among affected carriers included LHON, severe visual impairment, blindness, mild visual impairment, moderate visual impairment, onset unknown, visual loss, lHON\-plus, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3460 | m.3460G\>A | [G3460A\-F1](https://mitofam.com/doc/1415/) | Italy | LHON | 10 | 3 | 2002 | [12023431](https://pubmed.ncbi.nlm.nih.gov/12023431/) | Supplemental evidence PMID 17652639\. |
| 2 | 3460 | m.3460G\>A | [G3460A\-F2](https://mitofam.com/doc/1416/) | Italy | LHON\-plus | 0 | 1 | 2008 | [18216301](https://pubmed.ncbi.nlm.nih.gov/18216301/) |  |
| 3 | 3460 | m.3460G\>A | G3460A\-F3 | UK | LHON | 0 | 0 | 2008 | [18562849](https://pubmed.ncbi.nlm.nih.gov/18562849/) |  |
| 4 | 3460 | m.3460G\>A | G3460A\-F4 | India | LHON | 0 | 0 | 2010 | [20454697](https://pubmed.ncbi.nlm.nih.gov/20454697/) |  |
| 5 | 3460 | m.3460G\>A | [G3460A\-F5](https://mitofam.com/doc/1417/) | Italy | LHON | 7 | 0 | 2018 | [30053855](https://pubmed.ncbi.nlm.nih.gov/30053855/) |  |
| 6 | 3460 | m.3460G\>A | G3460A\-F6 | Brazil | LHON | 0 | 0 | 2021 | [33584522](https://pubmed.ncbi.nlm.nih.gov/33584522/) |  |
| 7 | 3460 | m.3460G\>A | G3460A\-F7 | Brazil | LHON | 0 | 0 | 2021 | [33584522](https://pubmed.ncbi.nlm.nih.gov/33584522/) |  |
| 8 | 3460 | m.3460G\>A | G3460A\-F8 | Brazil | LHON | 0 | 0 | 2021 | [33584522](https://pubmed.ncbi.nlm.nih.gov/33584522/) |  |
| 9 | 3460 | m.3460G\>A | G3460A\-F9 | Canada | LHON | 0 | 0 | 2022 | [35892476](https://pubmed.ncbi.nlm.nih.gov/35892476/) |  |
| 10 | 3460 | m.3460G\>A | [G3460A\-F10 ](https://mitofam.com/doc/1418/)| China | LHON | 4 | 2 | 2007 | [17434142](https://pubmed.ncbi.nlm.nih.gov/17434142/) | Carrying A14693G |
| 11 | 3460 | m.3460G\>A |[ G3460A\-F11](https://mitofam.com/doc/1419/) | China | LHON | 7 | 1 | 2010 | [20053576](https://pubmed.ncbi.nlm.nih.gov/20053576/) | WZ28; haplogroup D5; homoplasmic G3460A. |
| 12 | 3460 | m.3460G\>A | [G3460A\-F12 ](https://mitofam.com/doc/1420/)| China | LHON | 23 | 0 | 2010 | [20053576](https://pubmed.ncbi.nlm.nih.gov/20053576/) | WZ29; haplogroup B5b; homoplasmic G3460A. |
| 13 | 3460 | m.3460G\>A | [G3460A\-F13](https://mitofam.com/doc/1421/) | China | LHON | 25 | 2 | 2010 | [20053576](https://pubmed.ncbi.nlm.nih.gov/20053576/) | WZ30; haplogroup R9; homoplasmic G3460A. |
| 14 | 3460 | m.3460G\>A | [G3460A\-F14 ](https://mitofam.com/doc/1422/)| China | LHON | 35 | 0 | 2010 | [20053576](https://pubmed.ncbi.nlm.nih.gov/20053576/) | WZ31; haplogroup F1; homoplasmic G3460A. |
| 15 | 3460 | m.3460G\>A | [G3460A\-F15](https://mitofam.com/doc/1423/) | China | LHON | 8 | 0 | 2010 | [20053576](https://pubmed.ncbi.nlm.nih.gov/20053576/) | WZ32; haplogroup C4a1; homoplasmic G3460A. |
| 16 | 3460 | m.3460G\>A | [G3460A\-F16](https://mitofam.com/doc/1424/) | China | LHON | 1 | 1 | 2010 | [20232220](https://pubmed.ncbi.nlm.nih.gov/20232220/) | Le268; haplogroup D4b2b; homoplasmic G3460A in proband. |
| 17 | 3460 | m.3460G\>A | [G3460A\-F17 ](https://mitofam.com/doc/1425/)| China | LHON | 14 | 1 | 2010 | [20232220](https://pubmed.ncbi.nlm.nih.gov/20232220/) | Le688; haplogroup B4d1; heteroplasmic G3460A up to 40% in proband. |
| 18 | 3460 | m.3460G\>A | [G3460A\-F18](https://mitofam.com/doc/1426/) | China | LHON | 7 | 2 | 2010 | [20232220](https://pubmed.ncbi.nlm.nih.gov/20232220/) | Le1027; haplogroup M12a; homoplasmic G3460A in proband. |
| 19 | 3460 | m.3460G\>A | [G3460A\-F19](https://mitofam.com/doc/1427/) | China | LHON | 7 | 2 | 2010 | [20232220](https://pubmed.ncbi.nlm.nih.gov/20232220/) | Le1037; haplogroup A5b; homoplasmic G3460A in proband. |
| 20 | 3460 | m.3460G\>A | G3460A\-F20 | China | LHON | 0 | 0 | 2010 | [20232220](https://pubmed.ncbi.nlm.nih.gov/20232220/) | Le228; sporadic; no family members accessed; haplogroup F2\. |
| 21 | 3460 | m.3460G\>A | G3460A\-F21 | China | LHON | 0 | 0 | 2010 | [20232220](https://pubmed.ncbi.nlm.nih.gov/20232220/) | Le1441; sporadic; no family members accessed; haplogroup D4b2\. |
| 22 | 3460 | m.3460G\>A | [G3460A\-F22](https://mitofam.com/doc/1428/) | Italy | LHON\-plus | 1 | 6 | 2018 | [30591017](https://pubmed.ncbi.nlm.nih.gov/30591017/) | Haplogroup H27 |

# 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 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-III1 | Fam | F | N | N | A | 56 | 56% | / | 24% | 36% (leukocytes) | Healthy |  |
| 2 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-IV1 | Fam | M | Y | Y | A | 33 | Homo | Homo | Homo | Homo (leukocytes/platelets/liver) | LHON; onset at 18 years |  |
| 3 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-IV2 | Fam | F | N | N | A | 25 | Homo | Homo | Homo | / | Healthy |  |
| 4 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-IV3 | Fam | F | N | N | A | 25 | Homo | / | Homo | / | Healthy |  |
| 5 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-III3 | Fam | F | N | Y | A | 64 | Homo | / | / | / | LHON |  |
| 6 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-III5 | Fam | M | N | N | A | 60 | 22% | / | / | / | Healthy |  |
| 7 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-III7 | Fam | M | N | N | A | 55 | 19% | / | / | / | Healthy |  |
| 8 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-III8 | Fam | M | N | N | A | 46 | 17% | / | / | / | Healthy |  |
| 9 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-III9 | Fam | M | N | N | A | 45 | Homo | / | / | / | Healthy |  |
| 10 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-III21 | Fam | F | N | Y | A | 73 | Homo | / | / | / | LHON |  |
| 11 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-IV7 | Fam | F | N | N | A | 46 | 66% | / | / | / | Healthy |  |
| 12 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-V1 | Fam | F | N | N | A | 26 | 74% | / | / | / | Healthy |  |
| 13 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-V2 | Fam | M | N | N | A | 20 | Homo | / | / | / | Healthy |  |
| 14 | 3460 | m.3460G\>A | G3460A\-F1 | G3460A\-F1\-V3 | Fam | M | N | Y | A | 17 | Homo | / | / | / | LHON |  |
| 15 | 3460 | m.3460G\>A | G3460A\-F2 | G3460A\-F2\-IV1 | Fam | M | Y | Y | A | 30 | Homo | Homo | / | / | LHON\-plus, onset at 10 years |  |
| 16 | 3460 | m.3460G\>A | G3460A\-F2 | G3460A\-F2\-IV2 | Fam | M | N | Y | A | ND | Homo | Homo | / | / | LHON\-plus |  |
| 17 | 3460 | m.3460G\>A | G3460A\-F3 | G3460A\-F3\-I1 | Uninf | M | Y | Y | A | 75 | Homo | / | / | / | LHON |  |
| 18 | 3460 | m.3460G\>A | G3460A\-F4 | G3460A\-F4\-I1 | Uninf | M | Y | Y | A | 21 | Homo | / | / | / | LHON |  |
| 19 | 3460 | m.3460G\>A | G3460A\-F5 | G3460A\-F5\-I2 | Uninf | F | N | N | A | ND | 30% | / | / | / | Healthy |  |
| 20 | 3460 | m.3460G\>A | G3460A\-F5 | G3460A\-F5\-II2 | Fam | F | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 21 | 3460 | m.3460G\>A | G3460A\-F5 | G3460A\-F5\-II3 | Fam | F | N | N | A | ND | 40% | / | / | / | Healthy |  |
| 22 | 3460 | m.3460G\>A | G3460A\-F5 | G3460A\-F5\-II5 | Fam | M | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 23 | 3460 | m.3460G\>A | G3460A\-F5 | G3460A\-F5\-III1 | Fam | M | Y | Y | A | 17 | Homo | / | / | / | LHON |  |
| 24 | 3460 | m.3460G\>A | G3460A\-F5 | G3460A\-F5\-III2 | Fam | M | N | N | A | ND | Homo | / | / | / | No reported visual loss |  |
| 25 | 3460 | m.3460G\>A | G3460A\-F5 | G3460A\-F5\-III3 | Fam | F | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 26 | 3460 | m.3460G\>A | G3460A\-F5 | G3460A\-F5\-III4 | Fam | M | N | N | A | ND | 40% | / | / | / | Healthy |  |
| 27 | 3460 | m.3460G\>A | G3460A\-F6 | G3460A\-F6\-I1 | Uninf | M | Y | Y | A | ND | Heteroplasmic | / | / | / | LHON |  |
| 28 | 3460 | m.3460G\>A | G3460A\-F7 | G3460A\-F7\-I1 | Uninf | M | Y | Y | A | 25 | Homo | / | / | / | LHON |  |
| 29 | 3460 | m.3460G\>A | G3460A\-F8 | G3460A\-F8\-I1 | Uninf | M | Y | Y | A | 31 | Homo | / | / | / | LHON |  |
| 30 | 3460 | m.3460G\>A | G3460A\-F9 | G3460A\-F9\-I1 | Uninf | M | Y | Y | A | 20\-25 | 96\.7\-98\.4% | / | / | / | LHON |  |
| 31 | 3460 | m.3460G\>A | G3460A\-F10 | G3460A\-F10\-II2 | Fam | F | N | Y | A | ND | Homo | / | / | / | LHON; severe visual impairment; onset 12 or 16 years not individually assigned | Carrying A14693G |
| 32 | 3460 | m.3460G\>A | G3460A\-F10 | G3460A\-F10\-II4 | Fam | F | N | N | A | ND | Homo | / | / | / | Healthy | Carrying A14693G |
| 33 | 3460 | m.3460G\>A | G3460A\-F10 | G3460A\-F10\-II6 | Fam | F | N | Y | A | ND | Homo | / | / | / | LHON; severe visual impairment; onset 12 or 16 years not individually assigned | Carrying A14693G |
| 34 | 3460 | m.3460G\>A | G3460A\-F10 | G3460A\-F10\-III1 | Fam | M | Y | Y | A | 14 | Homo | / | / | / | LHON; onset at 14 years; bilateral central vision loss | Carrying A14693G |
| 35 | 3460 | m.3460G\>A | G3460A\-F11 | G3460A\-F11\-I2 | Uninf | F | N | Y | A | 32 | Homo | / | / | / | LHON; moderate visual impairment | Age at test 32; onset 26\. |
| 36 | 3460 | m.3460G\>A | G3460A\-F11 | G3460A\-F11\-III3 | Fam | M | Y | Y | A | 16 | Homo | / | / | / | LHON; severe visual impairment | Age at test 16; onset 16\. |
| 37 | 3460 | m.3460G\>A | G3460A\-F12 | G3460A\-F12\-IV2 | Fam | M | Y | Y | A | 23 | Homo | / | / | / | LHON; mild visual impairment | Age at test 23; onset 22\. |
| 38 | 3460 | m.3460G\>A | G3460A\-F13 | G3460A\-F13\-III9 | Fam | F | N | Y | A | 25 | Homo | / | / | / | LHON; moderate visual impairment | Age at test 25; onset 24\. |
| 39 | 3460 | m.3460G\>A | G3460A\-F13 | G3460A\-F13\-IV2 | Fam | F | N | Y | A | 21 | Homo | / | / | / | LHON; mild visual impairment | Age at test 21; onset 20\. |
| 40 | 3460 | m.3460G\>A | G3460A\-F13 | G3460A\-F13\-IV8 | Fam | M | Y | Y | A | 18 | Homo | / | / | / | LHON; severe visual impairment | Age at test 18; onset 18\. |
| 41 | 3460 | m.3460G\>A | G3460A\-F14 | G3460A\-F14\-IV1 | Fam | M | Y | Y | A | 27 | Homo | / | / | / | LHON; mild visual impairment | Age at test 27; onset 25\. |
| 42 | 3460 | m.3460G\>A | G3460A\-F15 | G3460A\-F15\-III3 | Fam | M | Y | Y | A | 20 | Homo | / | / | / | LHON; moderate visual impairment | Age at test 20; onset 20\. |
| 43 | 3460 | m.3460G\>A | G3460A\-F16 | G3460A\-F16\-II1 | Fam | F | Y | Y | A | ND | Homo | / | / | / | LHON | Proband; complete mtDNA sequenced. |
| 44 | 3460 | m.3460G\>A | G3460A\-F16 | G3460A\-F16\-II2 | Fam | M | N | Y | A | ND | / | / | / | / | LHON | Affected in Fig.1; individual mutation load not reported. |
| 45 | 3460 | m.3460G\>A | G3460A\-F17 | G3460A\-F17\-III2 | Fam | M | N | Y | A | ND | / | / | / | / | LHON | Affected in Fig.1; individual mutation load not reported. |
| 46 | 3460 | m.3460G\>A | G3460A\-F17 | G3460A\-F17\-III6 | Fam | M | Y | Y | A | ND | 40% | / | / | / | LHON | Proband; heteroplasmic G3460A up to 40%. |
| 47 | 3460 | m.3460G\>A | G3460A\-F18 | G3460A\-F18\-II1 | Fam | M | N | Y | A | ND | / | / | / | / | LHON | Affected in Fig.1; individual mutation load not reported. |
| 48 | 3460 | m.3460G\>A | G3460A\-F18 | G3460A\-F18\-III2 | Fam | M | Y | Y | A | ND | Homo | / | / | / | LHON | Proband; complete mtDNA sequenced. |
| 49 | 3460 | m.3460G\>A | G3460A\-F18 | G3460A\-F18\-III5 | Fam | M | N | Y | A | ND | / | / | / | / | LHON | Affected in Fig.1; individual mutation load not reported. |
| 50 | 3460 | m.3460G\>A | G3460A\-F19 | G3460A\-F19\-II5 | Fam | F | N | Y | A | ND | / | / | / | / | LHON | Affected in Fig.1; individual mutation load not reported. |
| 51 | 3460 | m.3460G\>A | G3460A\-F19 | G3460A\-F19\-II7 | Fam | M | N | Y | A | ND | / | / | / | / | LHON | Affected in Fig.1; individual mutation load not reported. |
| 52 | 3460 | m.3460G\>A | G3460A\-F19 | G3460A\-F19\-III6 | Fam | M | Y | Y | A | ND | Homo | / | / | / | LHON | Proband; complete mtDNA sequenced. |
| 53 | 3460 | m.3460G\>A | G3460A\-F20 | G3460A\-F20\-I1 | Uninf | ND | Y | Y | A | ND | Homo | / | / | / | LHON | Sporadic proband; no family members accessed. |
| 54 | 3460 | m.3460G\>A | G3460A\-F21 | G3460A\-F21\-I1 | Uninf | ND | Y | Y | A | ND | Homo | / | / | / | LHON | Sporadic proband; no family members accessed. |
| 55 | 3460 | m.3460G\>A | G3460A\-F22 | G3460A\-F22\-I1 | Uninf | F | N | Y | A | ND | Heteroplasmic | / | / | / | LHON; visual loss; blindness; onset unknown |  |
| 56 | 3460 | m.3460G\>A | G3460A\-F22 | G3460A\-F22\-II1 | Fam | M | N | Y | A | ND | Homo | / | / | / | LHON; visual loss; blindness; headache; onset unknown |  |
| 57 | 3460 | m.3460G\>A | G3460A\-F22 | G3460A\-F22\-II2 | Fam | F | N | Y | A | ND | Homo | / | / | / | LHON; visual loss; blindness; psychiatric comorbidities; onset unknown |  |
| 58 | 3460 | m.3460G\>A | G3460A\-F22 | G3460A\-F22\-II3 | Fam | F | N | Y | A | ND | Homo | / | / | / | LHON; optic neuritis; vertigo; tremor; diplopia; onset at 30 years |  |
| 59 | 3460 | m.3460G\>A | G3460A\-F22 | G3460A\-F22\-III1 | Fam | F | N | Y | A | ND | Homo | / | / | / | LHON; optic neuritis; bilateral scotoma; headache; onset at 21 years |  |
| 60 | 3460 | m.3460G\>A | G3460A\-F22 | G3460A\-F22\-III2 | Fam | F | N | Y | A | ND | Homo | / | / | / | LHON; bilateral optic neuritis; monolateral scotoma left eye; blind right eye; onset at 9 years |  |
| 61 | 3460 | m.3460G\>A | G3460A\-F22 | G3460A\-F22\-III3 | Fam | F | N | N | A | ND | Heteroplasmic | / | / | / | No optic signs at ophthalmologic visit; headache |  |
| 62 | 3460 | m.3460G\>A | G3460A\-F22 | G3460A\-F22\-IV1 | Fam | F | Y | Y | A | 5 | Homo | / | / | / | Acute spinal cord lesion; no optic neuropathy; cutaneous mastocytosis | Haplogroup H27 |

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