MITOFAM Help and Documentation

# MITOFAM Help and Documentation

MITOFAM is a public family-centered database for mitochondrial DNA (mtDNA) variants. It is designed to help researchers, clinicians and genetic counselors review published family-level evidence for mtDNA variants, including maternal-line segregation, carrier status, tissue-specific mutant load and reported clinical features.

Public browsing of MITOFAM does not require login, registration or a password. Curator-only editing or contribution-management functions, if shown on the website interface, are not required for ordinary database use.

**Website:** https://mitofam.com  
**Contact:** mitofam@163.com  
**Recommended citation:** MITOFAM - A Pedigree Database for Mitochondrial DNA Variants. https://mitofam.com, 2026.

---

## 1. What information is included in MITOFAM?

MITOFAM organizes mtDNA evidence at four connected levels:

1. **Variant level** - a mtDNA variant, its position, locus and summary of reported pedigrees and carriers.
2. **Family/pedigree level** - a published or curated maternal family carrying the variant, with family-level disease, nationality, maternal-relative counts, publication information and a pedigree diagram when available.
3. **Carrier level** - individual carriers mapped within a family, with sex, proband status, affected status, survival status, age information, tissue-specific mutant load, clinical features and notes.
4. **Evidence level** - publication year, PMID/reference and curator notes linking each record to the original source.

### Current release [updated June 30, 2026\]

The current release contains literature-curated records from mtDNA rRNA, tRNA, protein-coding and non-coding/control-region loci.

| Category | Deduplicated PMIDs | mtDNA variants | Pedigrees / families | Carriers |
|---|---:|---:|---:|---:|
| RNA genes and regions | 1,009 | 350 | 2,019 | 5,171 |
| Protein-coding and non-coding/control regions | 1,329 | 320 | 1,920 | 3,702 |
| **Total** | **2,186** | **670** | **3,939** | **8,873** |

The total PMID count is deduplicated across categories. Counts may change as new publications are curated and existing records are updated.

---

## 2. How to browse MITOFAM

### 2.1 Start from the home page

From the MITOFAM home page, users can browse records by mtDNA locus and variant class. The main browsing categories are:

- **All Project** - all public MITOFAM records.
- **rRNA Variant** - variants in mitochondrial rRNA genes.
- **tRNA Variant** - variants in mitochondrial tRNA genes.
- **Coding & Non-Coding/Control Region Variants** - variants in protein-coding genes and non-coding/control regions.

Records can also be sorted by update date or alphabetically when the corresponding sort options are available on the page.

### 2.2 Open a gene or locus

Click a gene or locus name, such as **MT-RNR1**, **MT-TL1**, **MT-ND4**, **MT-ATP6** or **MT-CYB**, to view the associated variants and families. Variant entries are usually shown using a short notation in the navigation tree, for example **A1555G**. The full mtDNA notation is shown within the record, for example **m.1555A>G**.

### 2.3 Open a variant page

A variant page summarizes the curated evidence for one mtDNA variant. For example, a variant page may include:

- mtDNA position and full variant notation;
- affected gene or locus;
- molecule or region type, such as 12S rRNA, tRNA, protein-coding gene or control region;
- reported homoplasmy and heteroplasmy status;
- mitoTIP or other prediction fields when applicable;
- pathogenicity status derived from published literature or prediction sources;
- number of reported pedigrees;
- number of reported carriers;
- number and percentage of carriers with homoplasmy or heteroplasmy when reported;
- number and percentage of affected carriers when reported;
- a brief text summary of major reported clinical features;
- a list of linked family records.

Variant-level summaries are intended to help users quickly identify the scale and type of evidence available for a variant. They should not be interpreted as population prevalence, disease penetrance or clinical diagnostic criteria.

### 2.4 Open a family/pedigree page

A family page contains the detailed pedigree-level and carrier-level evidence for one family. A typical family page includes:

- a pedigree diagram, when the published source provides sufficient information;
- family-level information, including nationality, disease, number of affected and unaffected maternal relatives, publication year and PMID/reference;
- a carrier table listing individual carriers extracted from the source;
- tissue-specific mutant levels, such as blood, muscle, urine or other tissue values;
- clinical features and curator notes.

When a publication reports a pedigree but does not provide full information for every individual, MITOFAM records only the details that can be extracted. Family-level maternal-relative counts may therefore be larger than the number of individually listed carriers.

---

## 3. Field definitions

### 3.1 Variant-level fields

| Field | Meaning |
|---|---|
| **Position** | mtDNA nucleotide position displayed in MITOFAM. |
| **Variant** | mtDNA variant in m. notation, such as m.1555A>G. |
| **Locus** | mtDNA gene or genomic region where the variant is located. |
| **RNA / protein / region description** | Functional annotation of the locus, such as 12S rRNA, tRNA, protein-coding gene or control region. |
| **Homoplasmy** | Indicates that homoplasmic carriers have been reported for this variant. |
| **Heteroplasmy** | Indicates that heteroplasmic carriers have been reported for this variant. |
| **mitoTIP** | Prediction or annotation field when applicable to the variant type. “N/A” means that the field is not applicable or not available. |
| **Pathogenicity** | Pathogenicity status derived from published literature or bioinformatic predictions. This is not a final clinical classification and should be interpreted with the original evidence. |
| **Pedigree Information** | Summary of the number of curated pedigrees, carriers, carrier mutant-load status and affected status when available. |

### 3.2 Family-level fields

| Field | Meaning |
|---|---|
| **No.** | Row number in the displayed table. |
| **Position** | mtDNA nucleotide position. |
| **Variant** | mtDNA variant in m. notation. |
| **Family ID** | MITOFAM family identifier. It usually combines the variant name and a family number, such as A1555G-F10. |
| **Nationality** | Country or population origin reported for the family. If the source does not specify this information, it may be shown as ND or left blank. |
| **Diseases** | Disease or phenotype reported at the family level in the source publication. |
| **Unaffected Maternal Relatives** | Number of unaffected maternal-line relatives reported in the pedigree or source article. |
| **Affected Maternal Relatives** | Number of affected maternal-line relatives (excluding the proband) reported in the pedigree or source article. |
| **Publication Year** | Year of the source publication. |
| **PMID/Ref** | PubMed identifier or other reference identifier. PMID links lead to the corresponding PubMed record when available. |
| **Note** | Curator notes, original family names, source-specific comments or extraction limitations. |

### 3.3 Carrier-level fields

| Field | Meaning |
|---|---|
| **Carrier ID** | MITOFAM carrier identifier mapped to a family. It usually combines the family ID and pedigree position, such as A1555G-F10-III5. |
| **Type (Fam/De novo/Uninf)** | Inheritance category: familial, de novo or uninformative/uncertain. |
| **Gender (F/M)** | Sex reported in the source: female, male or ND if not determined. |
| **Proband (Y/N)** | Whether the carrier is the proband in the source report. |
| **Affected (Y/N)** | Whether the carrier is reported as clinically affected. ND means not determined or not clearly reported. |
| **Die/Alive (D/A)** | Reported survival status: deceased, alive or ND if not determined. |
| **Age** | Age information as reported by the source. Depending on the publication, this may represent age at examination, age at onset or age at diagnosis; the note field should be checked for context. |
| **Blood Mutant Level** | Mutant mtDNA level in blood, if reported. Values may be shown as a percentage, Homo, Hetero, ND or /. |
| **Muscle Mutant Level** | Mutant mtDNA level in muscle, if reported. |
| **Urine Mutant Level** | Mutant mtDNA level in urine or urinary epithelial cells, if reported. |
| **Other Mutant Level** | Mutant mtDNA level in another tissue or sample type, such as saliva, hair follicle or buccal cells, if reported. The sample type is described in the note when available. |
| **Clinical Features** | Clinical manifestations extracted from the source publication. Terms are curated from the article and standardized when possible. |
| **Note** | Additional extraction notes, original carrier ID, exposure information, uncertain details, duplicate-text warnings or other source-specific comments. |

---

## 4. Symbols, codes and abbreviations

### 4.1 Data codes

| Code | Meaning |
|---|---|
| **Homo** | Homoplasmy; the tested sample was reported as carrying only or nearly only mutant mtDNA. |
| **Hetero** | Heteroplasmy; the tested sample was reported as a mixture of mutant and wild-type mtDNA. |
| **ND / nd** | Not determined, not described or not clearly extractable from the source. |
| **/** | Not reported or not applicable for that field. |
| **Y / N** | Yes / No. |
| **F / M** | Female / Male. |
| **D / A** | Deceased / Alive. |
| **Fam** | Familial inheritance or maternally inherited family case. |
| **De novo** | Reported as a de novo event. |
| **Uninf** | Uninformative or insufficient inheritance evidence. |
| **PMID** | PubMed identifier. |

### 4.2 Common disease and phenotype abbreviations

| Abbreviation | Meaning |
|---|---|
| **AD** | Alzheimer disease. |
| **ADPD** | Alzheimer disease and Parkinson disease. |
| **CIPO** | Chronic intestinal pseudo-obstruction with myopathy and ophthalmoplegia. |
| **CPEO** | Chronic progressive external ophthalmoplegia. |
| **DEAF** | Maternally inherited deafness or aminoglycoside-induced deafness. |
| **DM** | Diabetes mellitus. |
| **DMDF** | Diabetes mellitus and deafness. |
| **FICP** | Fatal infantile cardiomyopathy plus, a MELAS-associated cardiomyopathy. |
| **KSS** | Kearns-Sayre syndrome. |
| **LDYT** | Leber hereditary optic neuropathy and dystonia. |
| **LHON** | Leber hereditary optic neuropathy. |
| **LIMM** | Lethal infantile mitochondrial myopathy. |
| **MELAS** | Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. |
| **MERRF** | Myoclonic epilepsy with ragged-red fibers. |
| **MHCM** | Maternally inherited hypertrophic cardiomyopathy. |
| **MM** | Mitochondrial myopathy. |
| **MMC** | Maternal myopathy and cardiomyopathy. |
| **NARP** | Neuropathy, ataxia and retinitis pigmentosa. |
| **PEM** | Progressive encephalopathy. |
| **SNHL** | Sensorineural hearing loss. |
| **PTA** | Pure-tone audiometry. |

---

## 5. How MITOFAM records are curated

MITOFAM records are manually curated from published literature and qualified submissions. The basic curation unit is the **variant-family-publication** record. A single publication may contain multiple variants or multiple families; each extractable family is curated separately when the source permits.

The curation workflow includes:

1. **Source identification** - identifying publications or submitted materials that describe families with mtDNA variants.
2. **Variant extraction** - recording mtDNA position, variant notation and locus.
3. **Family extraction** - recording family ID, country/population, disease, publication information and maternal-relative counts.
4. **Carrier extraction** - mapping individual carriers to family IDs and recording sex, proband status, affected status, tissue mutant load and clinical features when available.
5. **Pedigree reconstruction** - drawing or curating a pedigree diagram when the publication provides sufficient information.
6. **Evidence review** - checking consistency between the family table, carrier table, pedigree diagram and source article.
7. **Ambiguity handling** - recording uncertain, aggregate-only or unmappable information in the note field rather than over-interpreting the source.

When a publication provides only aggregate information, MITOFAM records the aggregate data at the family or variant level. Individual carrier rows are created only when individual-level evidence can be reliably mapped.

---

## 6. How to interpret MITOFAM data

MITOFAM is an evidence browser, not a diagnostic tool. Users should interpret each record together with the original article and relevant clinical, genetic and biochemical evidence.

Important points for interpretation:

- A variant-level affected percentage is calculated from the curated carriers with available affected-status information. It is not a population penetrance estimate.
- Family-level counts and carrier-level counts may differ because many publications report pedigree symbols or aggregate maternal-relative counts without individual-level details.
- Tissue mutant load can vary substantially across sample types. Blood, muscle, urine and other samples should not be treated as interchangeable.
- “Pathogenicity” fields summarize literature or prediction-based evidence and should not replace formal clinical variant interpretation.
- Clinical features are extracted from source publications and may reflect the terminology used by the original authors.
- Absence of a field value usually means that the source did not report the information clearly enough for extraction, not that the feature was absent.

---

## 7. Data access and reuse

Individual MITOFAM pages can be viewed freely online. Page-level export options, such as Markdown, Word or PDF export, are available on record pages.

For reuse of MITOFAM content, please cite MITOFAM and the original source publications. Unless otherwise noted, MITOFAM content is made available under a Creative Commons Attribution 4.0 License.

---

## 8. How to contribute a pedigree

MITOFAM welcomes additional published or ethically approved pedigree data. To submit a pedigree, please email mitofam@163.com with the following information:

- mtDNA variant, for example m.1555A>G or m.3243A>G;
- number of pedigree(s);
- nationality or population origin of the pedigree(s), if known;
- source article PMID or PDF;
- supporting documents, if applicable;
- confirmation that the data can be shared publicly through MITOFAM with appropriate attribution.

Submitted data should meet the following criteria:

1. At least one individual in the family has genetic confirmation of an mtDNA variant.
2. Clinical manifestations are described for affected individuals when available.
3. The clinical phenotype is suspected to be associated with the mtDNA variant.
4. For unpublished or newly submitted human data, appropriate ethical approval and informed consent must have been obtained.

All public MITOFAM records should be anonymized before display.

---

## 9. Frequently asked questions

### Do I need an account to use MITOFAM?

No. Public MITOFAM browsing is free and does not require login, registration or a password. Any curator-only or access-code functions are for data management and are not needed for public use.

### Why are some fields marked ND or /?

MITOFAM records only what can be extracted from the source. ND means not determined or not clearly reported. “/” means not reported or not applicable.

### Why does a family page show more affected maternal relatives than carrier rows?

Some publications provide a pedigree diagram or family summary but do not list individual genetic or clinical information for every relative. In such cases, MITOFAM records family-level counts and creates individual carrier rows only for extractable carriers.

### Can I use MITOFAM for clinical diagnosis?

MITOFAM may help users review published evidence, but it does not provide medical advice and is not intended for self-diagnosis. Clinical diagnosis, genetic counseling and treatment decisions should be made by qualified professionals using complete clinical and laboratory evidence.

### How should I cite MITOFAM?

Please cite: **MITOFAM - A Pedigree Database for Mitochondrial DNA Variants. https://mitofam.com, 2026.** Please also cite the original source publication when using data from a specific family or variant record.

### How do I report an error?

Please email mitofam@163.com with the page URL, variant name, family ID or carrier ID, and a short description of the possible error. If available, include the PMID or source evidence supporting the correction.

---

## 10. Contact

MITOFAM Team  
Mitochondrial Genetic Disease Prevention and Treatment Center  
Reproductive Medical Center, Department of Obstetrics and Gynecology  
The First Affiliated Hospital of Anhui Medical University  
Hefei, Anhui, China  
Email: mitofam@163.com