Is the first position in a chromosome counted as "0" or "1" for the purpose of determining genomic coordinates?
The first position in the chromosome is "1".
Is the "risk allele" for a given site-disease association available (or derivable from data) in the HGMD® database?
The allele associated with the HGMD phenotype is available in the "Mutnomen" table (mutBASE column). The wildBASE column is the wild-type nucleotide sequence (NULL for insertions) and the mutBASE column is the mutated nucleotide sequence (NULL for deletions). When looking at the core data tables (e.g. mutation, prom), the phenotype allele should be the variant allele.
Which strand are the sequences in the database taken from?
All sequence data (wild-type, mutated, and flanking bases) are given as they would appear on the strand which encodes the protein in question (i.e. the "coding" strand). For example, in the case of CM014827, the "Mutnomen" table lists wildBASE="T" and mutBASE="C" to indicate the T>C polymorphic change described in the referenced article. The strand encoding the STX1A gene is the minus strand on the assembly, so this substitution would be equivalent to an A>G change in the assembly sequence.
wildBASE and mutBASE sequence are obtained from the core mutation tables whilst the flanking sequence is derived from the assembly. The flanking sequence is converted into the complementary sequence if the mutation was described on the non-coding strand in the reference, so as to correspond to the coding strand. Therefore all data in HGMD are "coding strand" data.
How to find the location of mutations in a specific variant for genes with multiple splicing variants? Is the codon numbering system for different mutations in a gene consistent, i.e. is the numbering for different mutations all based on one splicing variant? If yes, where could I find the accession number of this mRNA splicing variant?
Codon numbering is consistent with the cDNA sequences provided (along with the NCBI accession numbers). HGMD mutations are mapped to these sequences.
How does the HGMD® database represent a simple, single-base insertion?
For all insertions, the start coordinate is one less than the end coordinate. Additionally, for insertions, wildBASE in the "Mutnomen" table is NULL and mutBASE represents the inserted bases located between the start and end coordinates. A risk allele of length one is an insertion of length one.
Is there is a way to get a SNP list for a gene, which is not a mutation causing disease?
HGMD records disease-causing mutations and disease-associated/functional polymorphisms.
Neutral polymorphism data are available in other databases (e.g. dbSNP and HapMap). dbSNP data were integrated into HGMD for for missense/nonsense SNPs only.
I have tried to open "Get map" under Mutation viewer for ACTA2. The window could not be open and every time when I tried to open "Get map", all windows were closed and had to re-login.
Maybe you have to install "Java Runtime Environment version 6" on your computer locally.
Does the HGMD® provide information of genomic polymorphisms in genes?
How does the HGMD® define an genomic alteration as mutation or
polymorphism?
Disease-associated/functional polymorphisms are included in HGMD. To be included as disease-associated, a statistically significant (p<0.05) association between the polymorphism and a clinical phenotype must have been reported.
In case no clinical phenotype is known to be associated with a polymorphic variant, but sufficient in vitro or in vivo expression/functional data have nevertheless been presented to indicate functional significance, then the variant will be included in HGMD.
NCBI dbSNP numbers (where identified) are also included in the comment field. A polymorphism is a mutation found at a frequency of >1% in any population.
Two new germinal mutations recently identified in our lab, are not reported in HGMD® database?
HGMD records disease-causing mutations published in the literature. At the moment, the only way to get these mutations into HGMD would be to publish them.
How frequently the HGMD® updates the mutation database?
HGMD has quarterly releases.
Is the article/paper identified by the PMID in an allmut record one of the studies that established the genetic association with the disease/phenotype? If multiple studies examined the variation, which study is given in the PMID field (e.g. the first published, the most authoritative, etc.)?
The HGMD® application lists multiple articles per allmut record. Will all papers specified for an allmut record be in agreement about the risk allele? In what database table/columns are these additional articles in stored?
Allmut should contain the first literature report. Additional references are stored in the "Extrarefs" table.
The "risk allele" will not always be the same between different literature reports (which will report different phenotypes and functional studies).
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