G13063A

# **General Information**

| **Position** | **13063** | **Variant** | **m.13063G\>A** | **Locus** | **MT\-ND5** | **Amino\-AcidChange** | **V243I** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **APOGEE2** | VUS | **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.13063G\>A** variant in MT\-ND5 has been reported in 2 pedigrees. To date, 10 carriers have been reported. Reported mutation loads ranged from 0% to 80%, with a median of 22\.5% overall; affected carriers showed mutation loads from 17\.9% to 80%, with a median of 47\.5%; 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 (80%) and fibroblasts (70%) than in blood (25%). The main clinical manifestations among affected carriers included adult\-onset ataxia, myopathy, excessive fragmentary hypnic myoclonus, gait instability, midbrain MRI lesion, paper states proven PYGM molecular defects and that this case neither supports nor refutes m.13063G\>A pathogenicity., slurred speech, and transient visual loss.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 13063 | m.13063G\>A | [G13063A\-F1](https://mitofam.com/doc/1343/) | Italy inferred | mitochondrial encephalopathy / ataxia | 8 | 0 | 2007 | [17535832](https://pubmed.ncbi.nlm.nih.gov/17535832/) | Pedigree recheck added three direct maternal\-line relatives with leukocyte load 0 from Fig. 1C; their descendants are excluded because each L\=0 person is a branch stop. |
| 2 | 13063 | m.13063G\>A | G13063A\-F2 | USA inferred | myopathy with alternate PYGM molecular defects | 0 | 0 | 2020 | [32652755](https://pubmed.ncbi.nlm.nih.gov/32652755/) | Only m.13063G\>A has an original target\-positive subject in this PMID; other target alleles should not generate carrier rows from this paper.; Baylor new case, m.13063G\>A; pages 5,7,8,9,12; Table 3 and Table 4 plus section 3\.1\.1; USA inferred from Baylor College of Medicine/Baylor Genetics corresponding affiliation; subjects are clinical diagnostic\-lab cases unless otherwise stated. |

# **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 | 13063 | m.13063G\>A | G13063A\-F1 | G13063A\-F1\-III1 | Fam | M | Y | Y | A | 32 years (onset) | 25% | 80% | / | 70%(F) | Adult\-onset ataxia; transient visual loss; gait instability; slurred speech; excessive fragmentary hypnic myoclonus; midbrain MRI lesion | text and Fig.1C; Source: Patient 6 proband; Ragged\-red fibers; complex I deficiency. |
| 2 | 13063 | m.13063G\>A | G13063A\-F1 | G13063A\-F1\-II1 | Fam | F | N | ND | A | ND | 40% | / | / | / | ND | Provisional label from pedigree figure; relation inferred as maternal relative/mother.; Fig.1C rendered page 3; Source: Fig.1C maternal relative / mother; Clinical status not described. |
| 3 | 13063 | m.13063G\>A | G13063A\-F1 | G13063A\-F1\-III2 | Fam | F | N | ND | A | ND | 40% | / | / | / | ND | Provisional label from pedigree figure.; Fig.1C rendered page 3; Source: Fig.1C sibling/sister 1; Clinical status not described. |
| 4 | 13063 | m.13063G\>A | G13063A\-F1 | G13063A\-F1\-III3 | Fam | F | N | ND | A | ND | 30% | / | / | / | ND | Provisional label from pedigree figure.; Fig.1C rendered page 3; Source: Fig.1C sibling/sister 2; Clinical status not described. |
| 5 | 13063 | m.13063G\>A | G13063A\-F1 | G13063A\-F1\-III4 | Fam | F | N | ND | A | ND | 20% | / | / | / | ND | Provisional label from pedigree figure.; Fig.1C rendered page 3; Source: Fig.1C sibling/sister 3; Clinical status not described. |
| 6 | 13063 | m.13063G\>A | G13063A\-F1 | G13063A\-F1\-I2 | Fam | F | N | ND | A | ND | \<6% | / | / | / | ND | Provisional label from pedigree figure.; Fig.1C rendered page 3; Source: Fig.1C maternal ancestor; Clinical status not described. |
| 7 | 13063 | m.13063G\>A | G13063A\-F1 | G13063A\-F1\-II3 | Fam | M | N | N | ND | ND | 0% | / | / | / | Healthy | Leukocyte load 0 in direct maternal\-line child of low\-level target\-positive maternal ancestor; branch stop for descendants. |
| 8 | 13063 | m.13063G\>A | G13063A\-F1 | G13063A\-F1\-II4 | Fam | F | N | N | ND | ND | 0% | / | / | / | Healthy | Leukocyte load 0 in direct maternal\-line child of low\-level target\-positive maternal ancestor; branch stop for descendants. |
| 9 | 13063 | m.13063G\>A | G13063A\-F1 | G13063A\-F1\-II5 | Fam | F | N | N | ND | ND | 0% | / | / | / | Healthy | Leukocyte load 0 in direct maternal\-line child of low\-level target\-positive maternal ancestor; branch stop for descendants. |
| 10 | 13063 | m.13063G\>A | G13063A\-F2 | G13063A\-F2\-P1 | Uninf | ND | N | Y | ND | ND | / | 17\.9% | / | / | Myopathy; paper states proven PYGM molecular defects and that this case neither supports nor refutes m.13063G\>A pathogenicity. | Target\-positive original clinical\-lab case but alternate diagnosis; do not use as strong pathogenicity evidence.; page 8 text: identified m.13063G\>A at 17\.9% in muscle of a myopathic patient with proven PYGM defects.; Source: myopathic patient with PYGM molecular defects |

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