G5538A

# General Information

| **Position** | **5538** | **Variant** | **M.5538G\>A** | **Locus** | **MT\-TW** | **RNA** | **TRNA Trp** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **MitoTIP** | 76\.70% | **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.5538G\>A** variant in MT\-TW has been reported in 2 pedigrees. To date, 3 carriers have been reported. Reported mutation loads ranged from 2% to 65%, with a median of 5% overall; affected carriers showed mutation loads from 2% to 65%, with a median of 5%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (65%) than in blood (5%), urine (5%), and bone marrow (5%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (20%) and urine (5%) than in blood (2%). The main clinical manifestations among affected carriers included diabetes mellitus, fSGS\-associated ESRD, late\-onset myoclonic epilepsy, bilateral cataracts, developmental delay and neurologic changes, diabetes, hearing loss, history of hypothyroidism, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 5538 | M.5538G\>A | [G5538A\-F1](https://mitofam.com/doc/876/) | Italy | Late\-onset encephalomyopathy | 2 | 1 | 2010 | [20708751](https://pubmed.ncbi.nlm.nih.gov/20708751/) |  |
| 2 | 5538 | M.5538G\>A | G5538A\-F2 | USA | FSGS\-associated ESRD | ND | ND | 2017 | [29043143](https://pubmed.ncbi.nlm.nih.gov/29043143/) |  |

# 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 | 5538 | M.5538G\>A | G5538A\-F1 | G5538A\-F1\-II1 | Fam | F | Y | Y | A | 51 | 5% | 65% | 5% | 5%(BM) | Late\-onset myoclonic epilepsy,bilateral cataracts,pigmentary retinopathy,hypothyroidism,mild myopathy |  |
| 2 | 5538 | M.5538G\>A | G5538A\-F1 | G5538A\-F1\-I2 | Uninf | F | N | Y | A | 74 | 2% | 20% | 5% | / | Diabetes mellitus,history of hypothyroidism |  |
| 3 | 5538 | M.5538G\>A | G5538A\-F2 | G5538A\-F2\-P1 | Uninf | M | Y | Y | A | 34 | 30% | / | / | / | FSGS\-associated ESRD, diabetes, hearing loss, developmental delay and neurologic changes |  |

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