T9957C

# **General Information**

| **Position** | **9957** | **Variant** | **m.9957T\>C** | **Locus** | **MT\-CO3** | **Amino\-AcidChange** | **F251L** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.9957T\>C** variant in MT\-CO3 has been reported in 5 pedigrees. To date, 10 carriers have been reported. Homoplasmy was reported in 3/10 carriers (30%), and 8/10 carriers (80%) were affected. The main clinical manifestations among affected carriers included MELAS, hypertrophic cardiomyopathy with end\-stage congestive heart failure, bilateral cataracts, complete AV block with permanent pacemaker, heart transplantation, short stature, asymmetrical HCM, CPEO, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 9957 | m.9957T\>C | [T9957C\-F1](https://mitofam.com/doc/1685/) | Italy | Hypertrophic cardiomyopathy with late congestive heart failure | 1 | 4 | 1998 | [10065021](https://pubmed.ncbi.nlm.nih.gov/10065021/) | b\-MHC gene mutation |
| 2 | 9957 | m.9957T\>C | T9957C\-F2 | Saudi Arabia | Non\-arteritic ischemic optic neuropathy; seizures | ND | ND | 2005 | [15823923](https://pubmed.ncbi.nlm.nih.gov/15823923/) |  |
| 3 | 9957 | m.9957T\>C | [T9957C\-F3](https://mitofam.com/doc/1686/) | Korea | MELAS; cataract | 0 | 1 | 2008 | [18587274](https://pubmed.ncbi.nlm.nih.gov/18587274/) |  |
| 4 | 9957 | m.9957T\>C | T9957C\-F4 | Taiwan | Chronic progressive external ophthalmoplegia; corpus callosum agenesis; mental retardation | 1 | 2 | 2011 | [21249588](https://pubmed.ncbi.nlm.nih.gov/21249588/) |  |
| 5 | 9957 | m.9957T\>C | [T9957C\-F5](https://mitofam.com/doc/1687/) | USA | MELAS | 2 | 0 | 1995 | [7496173](https://pubmed.ncbi.nlm.nih.gov/7496173/) |  |

# **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 | 9957 | m.9957T\>C | T9957C\-F1 | T9957C\-F1\-II1 | Fam | F | ND | Y | A | 55 | 45% | 70% | / | 64%(heart) | Hypertrophic cardiomyopathy with end\-stage congestive heart failure; complete AV block with permanent pacemaker; heart transplantation | b\-MHC gene mutation |
| 2 | 9957 | m.9957T\>C | T9957C\-F1 | T9957C\-F1\-III1 | Fam | M | ND | Y | D | 31 | 48% | 82% | / | 92%(heart) | Hypertrophic cardiomyopathy with end\-stage congestive heart failure; complete AV block with permanent pacemaker; heart transplantation; died of sepsis after transplant | b\-MHC gene mutation |
| 3 | 9957 | m.9957T\>C | T9957C\-F1 | T9957C\-F1\-III2 | Fam | F | N | Y | A | 31 | / | / | / | / | Asymmetrical HCM; supraventricular tachycardia; transcatheter radiofrequency ablation; calcium channel blocker treatment | b\-MHC gene mutation |
| 4 | 9957 | m.9957T\>C | T9957C\-F2 | T9957C\-F2\-P1 | Uninf | M | Y | Y | ND | 76 | Homo | / | / | skin Homo; BM Homo | NAION with bilateral optic nerve disease, seizures, hypertension, elevated homocysteine; no MELAS features |  |
| 5 | 9957 | m.9957T\>C | T9957C\-F3 | T9957C\-F3\-II1 | Fam | M | Y | Y | ND | 25 | Homo | Homo | / | / | MELAS; seizure; diabetes; hypothyroidism; short stature; migraine; bilateral cataracts; ragged\-red fibers |  |
| 6 | 9957 | m.9957T\>C | T9957C\-F3 | T9957C\-F3\-I1 | Uninf | F | N | Y | ND | 54 | Homo | / | / | / | MELAS/cataract spectrum; short stature; recurrent migraine; bilateral cataracts; elevated lactate; MRI abnormalities |  |
| 7 | 9957 | m.9957T\>C | T9957C\-F4 | T9957C\-F4\-I1 | Uninf | F | Y | Y | ND | 45 | / | / | / | / | CPEO, bilateral ptosis, external ophthalmoplegia, mental retardation, poor visual acuity, mild limb weakness, generalized hyporeflexia, corpus callosum agenesis |  |
| 8 | 9957 | m.9957T\>C | T9957C\-F5 | T9957C\-F5\-I1 | Uninf | M | Y | Y | ND | 11 | 60% | 81% | / | / | MELAS; stroke\-like episodes; blindness; ptosis; hearing loss; lactic acidosis |  |
| 9 | 9957 | m.9957T\>C | T9957C\-F5 | T9957C\-F5\-I2 | Uninf | F | N | N | ND | ND | 50% | / | / | / | Asymptomatic |  |
| 10 | 9957 | m.9957T\>C | T9957C\-F5 | T9957C\-F5\-II1 | Fam | M | N | N | ND | ND | / | / | / | / | No history of neurological disorders |  |

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