Variant data provided by Mitomap on 2022-08-12
Info for variant 3273T>:
MITOMAP: Reported Mitochondrial DNA Base Substitution Diseases: rRNA/tRNA Variants | |||||||||||
| Nucleotide Position | Locus | Nucleotide Change† | Mitomap Frequency‡ in 56910 FL Seqs | gnomAD 3.1 Frequency‡‡ (count/total) | Helix Frequency‡‡‡ in 195983 seqs | Refs | Conservation | TOOLS †† | Homoplasmy/ Heteroplasmy | Disease | Mitomap Status ♣ |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 3273 | MT-TL1 | T-del (=T3271d) (tRNA Leu (UUR)) | 0 0.000% | NR | NR | 3 refs | 97.78% | MitoTIP: Pathogenic HmtVar: | -/+ | PEM / retinal dystrophy in MELAS | Cfrm |
† HGVS 3' Rule
We have standardized our variant notation to follow the 3' rule of HGVS (see their statement below). For your reference, we also show previously reported alternative notations in red.
Quote from HGVS: "For deletions, duplications and insertions the most 3' position possible is arbitrarily assigned to have been changed. This rule also applies to variants in single residue stretches (mono-nucleotide or amino acid) or tandem repeats."
‡ Mitomap Frequency and High Frequency Haplogroup Flags
The current haplogroup lineage distribution of Mitomap's 56910 sequences is N: 68%; L: 10%; M: 20%.
Variants found in haplogroups at 50% or higher are marked with 
. You may click a flagged link to see the high-scoring haplogroups. For detailed info about the high frequency haplogroup flag, please check the calculation criteria.
‡‡ gnomAD v3.1 Frequency
The current haplogroup lineage distribution of gnomAD's 56434 sequences is N: 70%; L: 25%; M: 5%.
- The Genome Aggregation Database (gnomAD) aggregates exome and genome sequencing data from a wide variety of large-scale sequencing projects. It is available at https://gnomad.broadinstitute.org/. The mitochondrial DNA data shared here is from gnomAD v3.1, with their permission.
- Homoplasmic counts are used in the main table for comparison with Mitomap. GnomAD also provides heteroplasmy data down to a 10% cutoff.
- A count of "NR" indicates No Record in the database.
- Please be aware of the relatively low representation of lineage M ("Asian") haplogroups when comparing to other datasets.
‡‡‡ Helix Frequency
The current haplogroup lineage distribution of Helix's 195893 sequences is N: 91%; L+M: 9%.
- The Helix population database is a variant catalog from ~196,000 buccal swab sequences primarily from ancestry services or broad general population surveys. The Helix data is reported with permission from Bolze et al. 2020, bioRxiv 798264 (see the article linked above).
- Homoplasmic counts are used in the main table for comparison with Mitomap. Helix also provides heteroplasmy data down to a ~1% cutoff (lowest=0.7%).
- A count of "NR" indicates No Record in the database.
- Due to privacy agreements, individual sequences are not publicly available and haplogroups are only reported at the top single-letter level (A-K, L0-L6, M-Z).
- Please be aware of the extremely high lineage N ("Eurasian") haplogroups when comparing to other datasets. Mitomap's estimation of the N, L, and M lineage distribution in Helix is 91.2%, 4.2%, and 4.6%, respectively.
♦ Amino Acid Change
Amino acid changes for variants in protein genes are predicted according to the human mitochondrial genetic code.
†† TOOLSIf available, data in this column are from the tools MitoTIP, HmtVar and/or APOGEE.
- tRNA mutations:
- MitoTIP:
For information about the predictive Mito TIP scoring for tRNA variants, please see Mito TIP Info.
- confirmed pathogenic
- likely pathogenic
- possibly pathogenic
- possibly benign
- likely benign
- frequency alert
- HmtVar: A score ≥0.35 is rated pathogenic by HmtVar. For more information see https://www.hmtvar.uniba.it
- Non-synonymous coding mutations:
- APOGEE: This is a consensus classifier by MitImpact which analyzes and combines input from 13 independent pathogenicity predictors and 6 meta-predictors. It is available for direct use at https://mitimpact.css-mendel.it/.
APOGEE Consensus APOGEE Scoring Mitomap Notation P >0.75 likely pathogenic P >0.50-0.75 possibly pathogenic N >0.25-0.50 neutral/possibly benign N 0-0.25 neutral/likely benign
- APOGEE: This is a consensus classifier by MitImpact which analyzes and combines input from 13 independent pathogenicity predictors and 6 meta-predictors. It is available for direct use at https://mitimpact.css-mendel.it/.
♣ ClinGen Pathogenicity Rating NEW
As a member of the mtDNA Variant Curation Expert Panel for ClinGen, we are adding the calculated ClinGen pathogenicity ratings after VCEP curation. This will be shown in brackets in the Mitomap Status column, for example, "Reported [VUS]", "Cfrm [LP]", etc., as the ClinGen scoring becomes available. The ClinGen VCEP may update this scoring from time to time if additional supporting evidence is published. The following abbreviations are used: B, Benign; LB, Likely Benign; VUS, Variant of Uncertain Significance; LP, Likely Pathogenic; P, Pathogenic. The criteria used in the ClinGen curations may be found in McCormick et al, 2020, DOI: 10.1002/humu.24107. Note that the ClinGen scoring gives fewer points than Mitomap does for many types of evidence, e.g., cybrid & other functional studies, in-silico tools, absence in large databases, heteroplasmy, de-novo requirements, and case numbers.
*Other FootnotesFull Length (FL) sequences are classified into three subsets: aDNA for ancient DNA, CancerCL for cancer, tumor, other abnormal tissues, or cell line studies, and Main for the rest. The total variant count is broken out into these three subsets in this column and shown in the format of Total: Main/aDNA/CancerCL (+CR seqs, if any). Clicking on the count link in the GB Sequences column will display a table with all sequence IDs and haplotypes. Each sequence has a further link to full SNP details provided by Mitomaster.
The current sequence counts are from two sets of human mitochondrial sequences collected from GenBank on Jul 01, 2022. These sets consist of:
- 56,910 Full Length (FL) sequences (>15.4 kb)
- FL.Main: 51,316
- FL.aDNA: 1,477
- FL.CancerCL: 1,801 (616 cancer + 1,185 cell lines)
- 78,504 Control Region (CR) only sequences (0.4-1.6 kb)
All sequences are pre-loaded into Mitomaster and represent almost all haplogroups known to date. We update and refine this set of sequences on a regular basis. As a caveat, please note that GenBank sequences may not be of equal quality (Yao, et al, 2009), that some of these sequences are from individuals with past, current or future disease, and that this portion of our data set has not been hand-curated by Mitomap.
For more details about the current GenBank sequence set, including haplogroup distribution with sequences and variants for each group, please see GenBank Frequency Info.
For the corrections made in 1999 by Andrews et al to the original Cambridge sequence, see this summary table. Due to rare polymorphisms in the reference sequence, some "variants" are present at more than 80% frequency in one or more of the three major mtDNA lineages. To see a listing of these common variants, please see Mitomap's tabulation of the most prevalent mtDNA variants along with its companion table of top level phylogenetic branch markers.
All nucleotide changes are reported as L-strand substitutions.
Variants reported in patients, but not assigned a "Cfrm" status of pathogenicity by Mitomap, may possibly be included in both the disease variants and general variants tables. Once Mitomap assigns a "Cfrm" status of pathogenicity to a variant, that variant will only be listed in the disease table.