G3697A

# General Information

| **Position** | **3697** | **Variant** | **m.3697G\>A** | **Locus** | **MT\-ND1** | **Amino\-AcidChange** | **G131S** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | Pathogenic | **Pathogenicity** | Cfrm \[LP] |

"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.3697G\>A** variant in MT\-ND1 has been reported in 5 pedigrees. To date, 22 carriers have been reported. Homoplasmy was reported in 9/22 carriers (40\.9%), and 13/22 carriers (59\.1%) were affected. In one affected carrier, the mutation was undetectable in muscle (0%) but exceeded 20% in blood (88%). The main clinical manifestations among affected carriers included spastic dystonia, leigh syndrome, bilateral putaminal lesions, putaminal lesion, LHON, left limb rigidity, leigh syndrome with complex I defect, right limbs clumsy, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3697 | m.3697G\>A | G3697A\-F1 | Japan | Leigh syndrome | 1 | 2 | 2014 | [24830958](https://pubmed.ncbi.nlm.nih.gov/24830958/) |  |
| 2 | 3697 | m.3697G\>A | G3697A\-F2 | Japan | Leigh syndrome | 0 | 0 | 2017 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 3 | 3697 | m.3697G\>A | [G3697A\-F3](https://mitofam.com/doc/1449/) | China | Bilateral striatal necrosis | 4 | 6 | 2019 | [30623604](https://pubmed.ncbi.nlm.nih.gov/30623604/) |  |
| 4 | 3697 | m.3697G\>A | [G3697A\-F4 ](https://mitofam.com/doc/1450/)| China | Leigh syndrome | 3 | 0 | 2021 | [34802141](https://pubmed.ncbi.nlm.nih.gov/34802141/) |  |
| 5 | 3697 | m.3697G\>A |[ G3697A\-F5](https://mitofam.com/doc/1451/) | Netherlands | LHON / spastic dystonia | 1 | 1 | 2007 | [17562939](https://pubmed.ncbi.nlm.nih.gov/17562939/) | Haplogroup T. |

# 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 | 3697 | m.3697G\>A | G3697A\-F1 | G3697A\-F1\-I2 | Uninf | F | N | N | A | ND | Heteroplasmic | / | / | / | Healthy |  |
| 2 | 3697 | m.3697G\>A | G3697A\-F1 | G3697A\-F1\-II1 | Fam | F | Y | Y | A | 9 | Homo | / | / | / | Leigh syndrome |  |
| 3 | 3697 | m.3697G\>A | G3697A\-F1 | G3697A\-F1\-II2 | Fam | M | N | Y | A | 7 | Homo | / | / | / | Leigh syndrome |  |
| 4 | 3697 | m.3697G\>A | G3697A\-F1 | G3697A\-F1\-II3 | Fam | F | N | Y | A | 5 | Homo | / | / | / | Leigh syndrome |  |
| 5 | 3697 | m.3697G\>A | G3697A\-F2 | G3697A\-F2\-I1 | Uninf | ND | Y | Y | A | ND | / | / | / | 100% (F) | Leigh syndrome with complex I defect |  |
| 6 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-II1 | Fam | F | N | Y | A | 50 | Homo | / | / | / | Right limbs clumsy, putaminal lesion |  |
| 7 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-II4 | Fam | F | N | Y | A | 47 | 99\.98% | / | / | / | Left limb rigidity, putaminal lesion |  |
| 8 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-II6 | Fam | F | N | N | A | 44 | Homo | / | / | / | Healthy |  |
| 9 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-III1 | Fam | F | N | N | A | 25 | Homo | / | / | / | Healthy |  |
| 10 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-III2 | Fam | M | N | Y | A | 23 | Homo | / | / | / | Spastic dystonia, bilateral putaminal lesions |  |
| 11 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-III3 | Fam | M | Y | Y | A | 20 | 99\.97% | / | 99\.96% | / | Spastic dystonia, bilateral putaminal lesions, moderate cognitive disability |  |
| 12 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-III4 | Fam | F | N | N | A | 18 | 99\.97% | / | / | / | Healthy |  |
| 13 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-III5 | Fam | M | N | Y | A | 16 | Homo | / | / | / | Spastic dystonia, bilateral putaminal and caudate lesions |  |
| 14 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-III6 | Fam | F | N | N | A | 9 | Homo | / | / | / | Healthy |  |
| 15 | 3697 | m.3697G\>A | G3697A\-F3 | G3697A\-F3\-III7 | Fam | M | N | Y | D | 17 | / | / | / | / | Spastic dystonia, bilateral putaminal lesions | No molecular testing in child; included because mother II6 has confirmed mutation load and child phenotype is explicitly reported. |
| 16 | 3697 | m.3697G\>A | G3697A\-F4 | G3697A\-F4\-I2 | Uninf | F | N | N | A | ND | 75\.16% | / | / | / | Healthy |  |
| 17 | 3697 | m.3697G\>A | G3697A\-F4 | G3697A\-F4\-II2 | Fam | F | N | N | A | 30 | 55\.97% | / | / | / | Healthy |  |
| 18 | 3697 | m.3697G\>A | G3697A\-F4 | G3697A\-F4\-II3 | Fam | M | N | N | A | ND | 57\.77% | / | / | / | Healthy |  |
| 19 | 3697 | m.3697G\>A | G3697A\-F4 | G3697A\-F4\-III1 | Fam | F | Y | Y | A | 2 | 99% | / | / | / | Leigh syndrome |  |
| 20 | 3697 | m.3697G\>A | G3697A\-F5 | G3697A\-F5\-I1 | Uninf | F | N | N | A | ND | 19% | 0% | / | / | Healthy |  |
| 21 | 3697 | m.3697G\>A | G3697A\-F5 | G3697A\-F5\-II1 | Fam | M | N | Y | A | 34 | 88% | 0% | / | / | Spastic dystonia, mental retardation, putamen hyperintensities |  |
| 22 | 3697 | m.3697G\>A | G3697A\-F5 | G3697A\-F5\-II2 | Fam | F | Y | Y | A | 35 | 56% | \>97% | / | / | LHON | Two healthy children aged 2 and 4 were reported but not tested. |

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