G8340A

# **General Information**

| **Position** | **8340** | **Variant** | **m.8340G\>A** | **Locus** | **MT\-TK** | **RNA** | **tRNA Lys** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | 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.8340G\>A** variant in MT\-TK has been reported in 7 pedigrees. To date, 8 carriers have been reported. Reported mutation loads ranged from 0% to 95%, with a median of 16\.5% overall; affected carriers showed mutation loads from 0\.3% to 95%, with a median of 25\.8%; unaffected carriers showed mutation loads from 0%, with a median of 0%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (59%), urine (7%), bone marrow (3%), ragged blue fibers (95%), and normal fibers (22%) than in blood (1%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in blood (11%), muscle (65%), other tissue (93\.1%), other tissue (29\.5%), and cox\-positive single muscle fibers (9%) than in cox\-deficient single muscle fibers (0\.3%). Similar tissue\-specific differences were observed in 1 additional carriers. The main clinical manifestations among affected carriers included CPEO, exercise intolerance, mitochondrial myopathy, ptosis, congenital microcephaly, pure myopathy, sensorineural deafness, bilateral cataracts, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 8340 | m.8340G\>A | G8340A\-F1 | Denmark | Mitochondrial myopathy; severe exercise intolerance | 0 | 0 | 2010 | [19941338](https://pubmed.ncbi.nlm.nih.gov/19941338/) | / |
| 2 | 8340 | m.8340G\>A | G8340A\-F2 | Danish | CPEO and exercise intolerance | 0 | 0 | 2013 | [23376095](https://pubmed.ncbi.nlm.nih.gov/23376095/) | / |
| 3 | 8340 | m.8340G\>A | G8340A\-F3 | Denmark | Myopathy, exercise intolerance, CPEO\-like | 0 | 0 | 2013 | [23838278](https://pubmed.ncbi.nlm.nih.gov/23838278/) | patient 9 |
| 4 | 8340 | m.8340G\>A | [G8340A\-F4](https://mitofam.com/doc/2200/) | Denmark | Pure myopathy; CPEO; exercise intolerance | 1 | 0 | 2013 | [24161205](https://pubmed.ncbi.nlm.nih.gov/24161205/) | / |
| 5 | 8340 | m.8340G\>A | G8340A\-F5 | Caucasian | Pigmentary retinopathy, rod\-cone dysfunction, sensorineural deafness, and epilepsy | 0 | 0 | 2017 | [28729369](https://pubmed.ncbi.nlm.nih.gov/28729369/) | / |
| 6 | 8340 | m.8340G\>A | G8340A\-F6 | Canada | CPEO\-like mitochondrial myopathy | 0 | 0 | 2018 | [29501485](https://pubmed.ncbi.nlm.nih.gov/29501485/) | / |
| 7 | 8340 | m.8340G\>A | G8340A\-F7 | United States | Congenital microcephaly, poor feeding, and poor weight gain | 0 | 0 | 2022 | [34969639](https://pubmed.ncbi.nlm.nih.gov/34969639/) | / |

# **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 | 8340 | m.8340G\>A | G8340A\-F1 | G8340A\-F1\-P1 | Uninf | ND | Y | Y | ND | ND | / | 84% | / | / | Mitochondrial myopathy; severe exercise intolerance | Cohort table only; age and sex not reported. PM group all had abnormal muscle histochemistry; Table 2 shows muscle RC complex I and IV reduction (CS\-corrected 31%/46%; complex II\-corrected 29%/42%). |
| 2 | 8340 | m.8340G\>A | G8340A\-F2 | G8340A\-F2\-P1 | Uninf | F | Y | Y | ND | 39 | / | 57% | / | / | CPEO; exercise intolerance | Cohort table subject 46\. |
| 3 | 8340 | m.8340G\>A | G8340A\-F3 | G8340A\-F3\-P1 | Uninf | F | Y | Y | A | 40 | / | 53% | / | / | CPEO; exercise intolerance | Original paper label patient 9; unrelated cohort subject. |
| 4 | 8340 | m.8340G\>A | G8340A\-F4 | G8340A\-F4\-III1 | De novo | F | Y | Y | A | 41 | 1% | 59% | 7% | 3% (BM); 95% (Ragged blue fibers); 22% (Normal fibers) | Pure myopathy; exercise intolerance; CPEO; ptosis; limb weakness | Original pedigree label \#3\.4; text reports average muscle 53%, while Fig. 1A labels M 59%. |
| 5 | 8340 | m.8340G\>A | G8340A\-F4 | G8340A\-F4\-IV1 | Fam | M | N | N | A | 16 | / | / | 0 | 0 (BM) | Healthy | Original label \#4\.1; urine and buccal epithelial cells negative. |
| 6 | 8340 | m.8340G\>A | G8340A\-F5 | G8340A\-F5\-P1 | De novo | M | Y | Y | A | 39 | 11% | 65% | / | 93\.12\+/\-0\.26% (COX\-deficient single muscle fibers); 29\.50\+/\-8\.97% (COX\-positive single muscle fibers) | Sensorineural deafness; nyctalopia; pigmentary retinopathy; rod\-cone dysfunction; bilateral cataracts; epilepsy; migraines; growth hormone deficiency; short stature | Mother: m.8340G\>A absent in buccal epithelia, urinary sediment, and blood. |
| 7 | 8340 | m.8340G\>A | G8340A\-F6 | G8340A\-F6\-P1 | De novo | F | Y | Y | A | 39 | 3\.3% | 92\.7% | / | / | Ptosis; ophthalmoparesis; mitochondrial myopathy; generalized weakness | Mother negative in blood and muscle. |
| 8 | 8340 | m.8340G\>A | G8340A\-F7 | G8340A\-F7\-P1 | De novo | ND | Y | Y | ND | 2\.4 | 2% | / | / | / | Congenital microcephaly; poor feeding; poor weight gain | Original paper label case 23; maternal tissue testing undetectable; WES nondiagnostic. |

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