A8348G

# **General Information**

| **Position** | **8348** | **Variant** | **m.8348A\>G** | **Locus** | **MT\-TK** | **RNA** | **tRNA Lys** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **mitoTIP** | 33\.80% | **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.8348A\>G** variant in MT\-TK has been reported in 3 pedigrees. To date, 4 carriers have been reported. Homoplasmy was reported in 1/4 carriers (25%), and 4/4 carriers (100%) were affected. The main clinical manifestations among affected carriers included easy fatigability, hypertrophic cardiomyopathy progressing to dilated cardiomyopathy, mild concentric left ventricular hypertrophy, SNHL, congestive heart failure, cortical atrophy, enlargement of the fourth ventricle, lactic acidosis, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 8348 | m.8348A\>G | [A8348G\-F1](https://mitofam.com/doc/2190/) | Japan | Cardiomyopathy | 1 | 1 | 2001 | [11446509](https://pubmed.ncbi.nlm.nih.gov/11446509/) | / |
| 2 | 8348 | m.8348A\>G | A8348G\-F2 | Japan | Mental retardation / lactic acidosis; no cardiomyopathy | 0 | 0 | 2006 | [16337222](https://pubmed.ncbi.nlm.nih.gov/16337222/) | Patient 39 |
| 3 | 8348 | m.8348A\>G | A8348G\-F3 | Japan | Sensorineural hearing loss | 0 | 2 | 2010 | [20111055](https://pubmed.ncbi.nlm.nih.gov/20111055/) | Pedigree shows affected mother and younger sister, but only proband has reported target molecular evidence. |

# **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 | 8348 | m.8348A\>G | A8348G\-F1 | A8348G\-F1\-II2 | Fam | M | N | Y | A | ND | Hetero; load NR | / | / | / | Mild concentric left ventricular hypertrophy; no cardiac symptoms | Blood mutant ratio was reported as higher than the proband, but no numeric value was given. |
| 2 | 8348 | m.8348A\>G | A8348G\-F1 | A8348G\-F1\-II1 | Fam | M | Y | Y | A | 46 | Hetero; load NR | / | / | Mutant dominant (Heart tissue) | Hypertrophic cardiomyopathy progressing to dilated cardiomyopathy; congestive heart failure; ventricular arrhythmias | m.8348A\>G detected in blood and heart tissue; no numeric load reported. |
| 3 | 8348 | m.8348A\>G | A8348G\-F2 | A8348G\-F2\-P1 | Uninf | M | Y | Y | ND | 12 | / | 34% | / | / | Easy fatigability; mild mental retardation from age 9 months; lactic acidosis; cortical atrophy; ventricular dilatation; enlargement of the fourth ventricle | Patient 39; Table 1 lists onset 9 months and negative family history; no cardiomyopathy; muscle respiratory chain enzyme activities showed complex I/IV decrease. |
| 4 | 8348 | m.8348A\>G | A8348G\-F3 | A8348G\-F3\-P1 | Fam | M | Y | Y | A | 6 | Homo | / | / | / | SNHL; onset age 3; no reported cardiac symptoms | Blood DNA screening; Figure 2 calls A8348G homoplasmic. Mother and sister have HL but no reported target mutation test. |

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