A9972C

# **General Information**

| **Position** | **9972** | **Variant** | **m.9972A\>C** | **Locus** | **MT\-CO3** | **Amino\-AcidChange** | **I256L** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **APOGEE2** | Likely\-benign | **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.9972A\>C** variant in MT\-CO3 has been reported in 1 pedigree. To date, 3 carriers have been reported. Reported mutation loads ranged from 0% to 99%, with a median of 3\.5% overall; affected carriers showed mutation loads from 0% to 99%, with a median of 5%; unaffected carriers showed mutation loads from 0\.1% to 1\.5%, with a median of 0\.8%. In one affected carrier, the mutation was undetectable in blood (0%) and hair (0%) but exceeded 20% in muscle (99%), cox\-negative fibers (96\.8%), and cox\-positive fibers (76\.3%). In one unaffected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in urine (1\.5%) than in blood (less than 0\.1%). The main clinical manifestations among affected carriers included APS2, growth retardation, diffuse muscle wasting, exercise intolerance, fatigue, lactic acidosis, leg pain, mitochondrial myopathy, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 9972 | m.9972A\>C | [A9972C\-F1](https://mitofam.com/doc/1664/) | Northern European ancestry | Exercise intolerance; autoimmune polyendocrinopathy type 2; mitochondrial myopathy | 2 | 0 | 2009 | [19460300](https://pubmed.ncbi.nlm.nih.gov/19460300/) |  |

# **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 | 9972 | m.9972A\>C | A9972C\-F1 | A9972C\-F1\-II2 | Fam | F | Y | Y | A | 12 | 0% | 99% | 5% | 5%(gastric cells); 2%(F); 0%(H); 96\.8%(COX\-negative fibers); 76\.26%(COX\-positive fibers) | Growth retardation, exercise intolerance, lactic acidosis, fatigue, leg pain, vomiting after exertion, diffuse muscle wasting, proximal weakness, APS2, mitochondrial myopathy |  |
| 2 | 9972 | m.9972A\>C | A9972C\-F1 | A9972C\-F1\-I1 | Uninf | F | N | N | A | ND | \<0\.1% | / | 1\.5% | / | No similarly affected relatives reported |  |
| 3 | 9972 | m.9972A\>C | A9972C\-F1 | A9972C\-F1\-II1 | Fam | F | N | N | A | ND | / | / | / | / | Completely asymptomatic |  |

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