T3398C

# **General Information**

| **Position** | **3398** | **Variant** | **m.3398T\>C** | **Locus** | **MT\-ND1** | **Amino\-AcidChange** | **M31T** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \- | **APOGEE2** | VUS\+ | **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.3398T\>C** variant in MT\-ND1 has been reported in 3 pedigrees. To date, 6 carriers have been reported. Homoplasmy was reported in 1/6 carriers (16\.7%), and 3/6 carriers (50%) were affected. The main clinical manifestations among affected carriers included exercise\-induced lactic acidosis, gestational diabetes mellitus (4 patients), lVHT Dilated cardiomyopathy with heart failure Axonal sensorimotor polyneuropathy Mitochondrial myopathy, MELAS, mitochondrial encephalomyopathy Multi\-system mitochondrial disorder Congenital sensorineural hearing loss Hypogonadism and gynaecomastia Focal proliferative glomerulonephritis → ESRD Left ventricular hypertrabeculation, vertical ophthalmoplegia High\-pitched voice Babinski's sign, cardiomyopathy and diabetes, and non\-compaction.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3398 | m.3398T\>C | T3398C\-F1 | Austria | Mitochondrial encephalomyopathy,Multi\-system mitochondrial disorder,Congenital sensorineural hearing loss,Hypogonadism and gynaecomastia | 4 | 0 | 2000 | [10894993](https://pubmed.ncbi.nlm.nih.gov/10894993/) | carrying T4216C,G15812A,A15662G |
| 2 | 3398 | m.3398T\>C | T3398C\-F2 | Germany | MELAS / cardiomyopathy / diabetes | 0 | 0 | 1996 | [8723687](https://pubmed.ncbi.nlm.nih.gov/8723687/) |  |
| 3 | 3398 | m.3398T\>C | T3398C\-F3 | Singapore | Gestational diabetes mellitus | 0 | 0 | 2000 | [10704697](https://pubmed.ncbi.nlm.nih.gov/10704697/) | Aggregate row represents four GDM patients; individual IDs not reported. |

# **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 | 3398 | m.3398T\>C | T3398C\-F1 | T3398C\-F1\-I2 | Uninf | F | N | N | A | 73 | \+ | / | / | / | healthy | carrying G15812A,A15662G |
| 2 | 3398 | m.3398T\>C | T3398C\-F1 | T3398C\-F1\-II2 | Fam | F | N | N | A | 52 | \+ | / | / | / | healthy | carrying G15812A,A15662G |
| 3 | 3398 | m.3398T\>C | T3398C\-F1 | T3398C\-F1\-III1 | Fam | M | Y | Y | A | 33 | / | \>75% | / | / | Mitochondrial encephalomyopathyMulti\-system mitochondrial disorderCongenital sensorineural hearing lossHypogonadism and gynaecomastiaFocal proliferative glomerulonephritis → ESRDLeft ventricular hypertrabeculation/non\-compaction, LVHTDilated cardiomyopathy with heart failureAxonal sensorimotor polyneuropathyMitochondrial myopathy;Vertical ophthalmoplegiaHigh\-pitched voiceBabinski's sign \+Exercise\-induced lactic acidosis | carrying T4216C,G15812A,A15662G |
| 4 | 3398 | m.3398T\>C | T3398C\-F1 | T3398C\-F1\-III2 | Fam | M | N | N | A | 28 | \+ | / | / | / | healthy | carrying G15812A,A15662G |
| 5 | 3398 | m.3398T\>C | T3398C\-F2 | T3398C\-F2\-I1 | Uninf | M | Y | Y | A | ND | Homo | / | / | / | MELAS, cardiomyopathy and diabetes | Carrying A3243G. |
| 6 | 3398 | m.3398T\>C | T3398C\-F3 | T3398C\-F3\-I1 | Uninf | F | ND | Y | A | 30\-34 | Heteroplasmic | / | / | / | Gestational diabetes mellitus (4 patients) | Aggregate row represents 4 GDM patients; fasting glucose and treatment were reported only as grouped ranges. |

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