G14846A

# **General Information**

| **Position** | **14846** | **Variant** | **m.14846G\>A** | **Locus** | **MT\-CYB** | **Amino\-AcidChange** | **G34S** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **APOGEE2** | Likely\-pathogenic | **Pathogenicity** | Reported \[VUS] |

"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.14846G\>A** variant in MT\-CYB has been reported in 1 pedigree. To date, 3 carriers have been reported. Reported mutation loads ranged from 0% to 98%, with a median of 0% overall; affected carriers showed mutation loads from 0% to 98%, with a median of 0%; unaffected carriers showed mutation loads from 0%, with a median of 0%. In one affected carrier, the mutation was undetectable in blood (0%), cultured myoblasts (0%), and fibroblasts (0%) but exceeded 20% in muscle (85%) and muscle (98%). The main clinical manifestations among affected carriers included exercise intolerance, dyspnea, hyperlactacidemia, masticatory fatigue, mild myopathy, and proximal limb weakness.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 14846 | m.14846G\>A | [G14846A\-F1](https://mitofam.com/doc/1932/) | USA | Exercise intolerance; masticatory fatigue; mitochondrial myopathy; complex III deficiency | 2 | 0 | 1999 | 10502593; support: 11506394, 11782982 | Later PMIDs are support\-only follow\-up of the same EO/Patient 2; two children tested negative. |

# **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 | 14846 | m.14846G\>A | G14846A\-F1 | G14846A\-F1\-I1 | De novo | F | Y | Y | A | 52 | 0 | 85%; 98% in later biopsy | / | 0% (cultured myoblasts); 0% (F) | Exercise intolerance; masticatory fatigue; proximal limb weakness; hyperlactacidemia; mild myopathy; dyspnea | Same EO/Patient 2 as support PMIDs 11506394 and 11782982; single\-fiber PCR RRF 91%, non\-RRF 17%. |
| 2 | 14846 | m.14846G\>A | G14846A\-F1 | G14846A\-F1\-II1 | Fam | ND | N | N | A | ND | 0 | / | / | 0% (cultured myoblasts); 0% (F) | Healthy | Negative\-tested child of target\-positive mother; branch stop for descendants. |
| 3 | 14846 | m.14846G\>A | G14846A\-F1 | G14846A\-F1\-II2 | Fam | ND | N | N | A | ND | 0 | / | / | 0% (cultured myoblasts); 0% (F) | Healthy | Negative\-tested child of target\-positive mother; branch stop for descendants. |

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