A13514G

# **General Information**

| **Position** | **13514** | **Variant** | **m.13514A\>G** | **Locus** | **MT\-ND5** | **Amino\-AcidChange** | **D393G** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **APOGEE2** | 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.13514A\>G** variant in MT\-ND5 has been reported in 7 pedigrees. To date, 10 carriers have been reported. Reported mutation loads ranged from 4% to 90%, with a median of 52\.5% overall; affected carriers showed mutation loads from 4% to 90%, with a median of 55%; unaffected carriers showed mutation loads from 5% to 57%, with a median of 8%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (70%) and fibroblasts (12%) than in blood (4%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in blood (50%) than in fibroblasts (20%). Similar tissue\-specific differences were observed in 1 additional carriers. The main clinical manifestations among affected carriers included leigh, mELAS\-like, optic atrophy, generalized epilepsy attributed to astrocytoma at 27, leigh MRI, leigh\-like syndrome with bilateral optic atrophy at 6 years, MELAS, mRI lesions, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 13514 | m.13514A\>G | A13514G\-F1 | Italy | MELAS | 0 | 5 | 2001 | [11198278](https://pubmed.ncbi.nlm.nih.gov/11198278/) |  |
| 2 | 13514 | m.13514A\>G | A13514G\-F2 | Italy | MELAS | 0 | 0 | 2001 | [11198278](https://pubmed.ncbi.nlm.nih.gov/11198278/) |  |
| 3 | 13514 | m.13514A\>G | A13514G\-F3 | France | multisystem mitochondrial disease with cardiomyopathy/nephropathy | 0 | 0 | 2003 | [14684687](https://pubmed.ncbi.nlm.nih.gov/14684687/) | Patient 7 |
| 4 | 13514 | m.13514A\>G | A13514G\-F4 | Italy | Leigh\-like syndrome / complex I deficiency | 0 | 0 | 2004 | [15576045](https://pubmed.ncbi.nlm.nih.gov/15576045/) | Patient 8 |
| 5 | 13514 | m.13514A\>G | [A13514G\-F5](https://mitofam.com/doc/1316/) | UK/Pakistani | Leigh syndrome / isolated complex I deficiency | 2 | 0 | 2011 | [21712854](https://pubmed.ncbi.nlm.nih.gov/21712854/) | consanguinity did not imply recessive inheritance; mtDNA mutation maternally transmitted.; Patient 1 family; pages 1\-3; UK/Pakistani family; clinical care in UK |
| 6 | 13514 | m.13514A\>G | A13514G\-F6 | France | mitochondrial disorder / Leigh spectrum | 0 | 0 | 2013 | [23847141](https://pubmed.ncbi.nlm.nih.gov/23847141/) | French cohort m.13514A\>G; Table 1; France; French Mitochondrial Disease Network cohort. |
| 7 | 13514 | m.13514A\>G | A13514G\-F7 | Italy | MELAS | 0 | 0 | 2020 | [32504279](https://pubmed.ncbi.nlm.nih.gov/32504279/) | Patient 51; Table 1 continued.; Italy; Siena/Pisa Italian adult MD cohort.; Source table labels gene as ND1 while position/variant correspond to MT\-ND5; highlighted for manual QC. |

# **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 | 13514 | m.13514A\>G | A13514G\-F1 | A13514G\-F1\-P1 | Uninf | M | Y | Y | A | 26 y | 4% | 70% | / | 12%(F) | MELAS\-like; visual loss; hearing loss; optic atrophy; tremor; myoclonus; cortical signs | Patient 1; Normal lactate and normal muscle biopsy. |
| 2 | 13514 | m.13514A\>G | A13514G\-F2 | A13514G\-F2\-P1 | Uninf | F | Y | Y | A | 18 y at major presentation | / | 55% | / | / | MELAS\-like; paresthesias; sudden visual loss; headaches; weakness; MRI lesions | Patient 2; High CSF lactate; muscle normal. |
| 3 | 13514 | m.13514A\>G | A13514G\-F3 | A13514G\-F3\-P1 | De novo | M | Y | Y | A | 35 years | / | / | / | 90%(Heart) | Generalized epilepsy attributed to astrocytoma at 27, tubulointerstitial nephropathy, hypertrophic cardiomyopathy, peripheral neuropathy, optic atrophy, mild psychomotor retardation and diabetes. |  |
| 4 | 13514 | m.13514A\>G | A13514G\-F4 | A13514G\-F4\-P1 | Uninf | ND | Y | Y | A | 6 years (onset) | 50% | / | / | 20%(F) | Leigh\-like syndrome with bilateral optic atrophy at 6 years, transient midbrain/basal nuclei MRI changes. | Patient 8 |
| 5 | 13514 | m.13514A\>G | A13514G\-F5 | A13514G\-F5\-III1 | Fam | F | Y | Y | D | 18 months onset; 30 months at death | / | 69% | / | 55%(F) | microcephaly; seizures; psychomotor/language delay; Leigh MRI; ventilatory failure | born to first\-cousin Pakistani parents; case report and results; Source: Patient 1 |
| 6 | 13514 | m.13514A\>G | A13514G\-F5 | A13514G\-F5\-II2 | Fam | F | N | N | ND | ND | 5% | / | 8% | 57%(BM) | Healthy | maternal transmission confirmed; results; Source: mother |
| 7 | 13514 | m.13514A\>G | A13514G\-F5 | A13514G\-F5\-III2 | Fam | M | N | N | ND | ND | / | / | / | / | Healthy | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 8 | 13514 | m.13514A\>G | A13514G\-F6 | A13514G\-F6\-P1 | Uninf | M | Y | Y | A | 1\-16 years | / | / | / | / | Ptosis; visual abnormality; leucopenia; Leigh | Anonymous aggregate row.; Table 1; Source: aggregate patient 1; Lipidosis/RRF; normal muscle and fibroblast respiratory chain. |
| 9 | 13514 | m.13514A\>G | A13514G\-F6 | A13514G\-F6\-P2 | Uninf | F | Y | Y | A | \<1 year | / | / | / | / | Psychomotor retardation; ataxia; hypotonia; liver involvement; postnatal growth retardation; Leigh | Anonymous aggregate row.; Table 1; Source: aggregate patient 2; Lipidosis; normal muscle/liver respiratory chain. |
| 10 | 13514 | m.13514A\>G | A13514G\-F7 | A13514G\-F7\-P1 | Uninf | F | Y | Y | A | 39 y | / | / | / | Positive(ND) | MELAS | Table labels gene as ND1 but m.13514A\>G is MT\-ND5 by workbook target; use allele as given in table.; Table 1 continued.; Source: Patient 51; ND1/MT\-ND5 source\-label discrepancy; position 13514 retained.; COX\-negative fibers 0\.8%; FGF21 75; GDF15 602\. |

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