G5540A

# General Information

| **Position** | **5540** | **Variant** | **M.5540G\>A** | **Locus** | **MT\-TW** | **RNA** | **TRNA Trp** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **MitoTIP** | 73\.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.5540G\>A** variant in MT\-TW has been reported in 3 pedigrees. To date, 3 carriers have been reported. Reported mutation loads ranged from 12% to 98%, with a median of 42\.7% overall; affected carriers showed mutation loads from 12% to 98%, with a median of 42\.7%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (51\.4%) than in blood (25\.6%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in m, age 28 (56%), m, age 41 (72%), urine (34%), and saliva (28%) than in blood (12%). The main clinical manifestations among affected carriers included early\-onset severe mitochondrial encephalomyopathy, mitochondrial encephalomyopathy, progressive ataxia of childhood onset, and spinocerebellar ataxia (SCA).

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 5540 | M.5540G\>A | G5540A\-F1 | Italy | Spinocerebellar ataxia (SCA) | ND | ND | 2000 | [10762520](https://pubmed.ncbi.nlm.nih.gov/10762520/) |  |
| 2 | 5540 | M.5540G\>A | G5540A\-F2 | USA | Early\-onset severe mitochondrial encephalomyopathy | 0 | 0 | 2014 | [25302159](https://pubmed.ncbi.nlm.nih.gov/25302159/) |  |
| 3 | 5540 | M.5540G\>A | G5540A\-F3 | UK | Mitochondrial encephalomyopathy, progressive ataxia of childhood onset | 4 | 0 | 2016 | [27618137](https://pubmed.ncbi.nlm.nih.gov/27618137/) |  |

# 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 | 5540 | M.5540G\>A | G5540A\-F1 | G5540A\-F1\-P1 | Uninf | F | Y | Y | D | 36 | / | 98% | / | / | Spinocerebellar ataxia (SCA) |  |
| 2 | 5540 | M.5540G\>A | G5540A\-F2 | G5540A\-F2\-P1 | De novo | F | Y | Y | ND | 10 | 25\.6% | 51\.4% | / | / | Early\-onset severe mitochondrial encephalomyopathy |  |
| 3 | 5540 | M.5540G\>A | G5540A\-F3 | G5540A\-F3\-II2 | De novo | F | Y | Y | ND | 45 | 12% | 56% (M, age 28\); 72% (M, age 41\) | 34% | 28%(Saliva) | Mitochondrial encephalomyopathy, progressive ataxia of childhood onset |  |

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