Introduction

The primary objective of this database is as a resource to help diagnostic laboratory scientists to interpret the significance of sequence variants in the ENG and ACVRL1 (ALK1) genes. By submitting the variants as described on this page, we should also be able to begin to collect frequency data for each. However, to make this database a more useful tool for clinicians and scientists alike, we encourage you to also submit phenotypic information of individuals with a variant in order that genotype/phenotype correlations may be studied in the future.

Explanation of data structure

For each variant, data is collected at 3 levels. These levels are organised into a pyramid: A single variant may be detected at a number of centres, with each centre recording the same variant in several, apparently unrelated, individuals. These levels appear on the screen as separate panels, with a different count for each.

Variant details: This top panel holds the details of any particular sequence variant. This is completed only once, at the time a novel variant is submitted to the database. This prevents multiple entries of the same variant appearing in the database list.

Centre submitting variant: The second panel records each centre that has submitted the particular variant, along with the method used to detect it. This section is completed the first time the variant is identified by a particular centre. To simplify the structure, it is recommended that the name of a single submitter be used for all entries from one centre. Once a centre has an entry here, all subsequent records of the same variant are entered without changing this information. However, if your centre uses more than one detection method (simultaneously or subsequently) you will need to create a separate record for each.

Clinical Phenotype: The lower panel should be filled in for each incidence (index case only) of the variant you are reporting. It is important to make an entry here, since this third panel will be used to 'count' the incidence of each variant. If no phenotypic data is available, or you do not wish to enter any clinical information, then just select "No phenotype information" from the "Details of index case" drop down menu.

Data entry

To submit an incidence of a sequence variant to the database, you must LOG-IN using your username and password. If you do not have these, or have forgotten them, please contact us.

To submit a novel sequence variant to the database:

1. Log-in and click [New Mutation].
2. Complete as many details as possible in the top panel (Variant Details). Variants should be described using the latest nomenclature described by the Human Genome Variation Society, which can be found here.
3. Click on "New" at the top right hand corner of the middle panel (Centre submitting variant), select the name of the submitter for your centre and enter details of your detection method.
4. Next, click on "New" at the top right hand corner of the lower panel (Clinical Phenotype). If no phenotypic data is available or you do not wish to enter any clinical information then please ensure that you select "No phenotype information" from the "Details of index case" drop down menu.
5. Finally, click "Save" to add the record to the database.

Additional entries of a sequence variant

First identification of a recorded variant at your centre.

To catalog another incidence of a variant that has already been submitted to the database by someone else:

1. Log-in and select [Mutations]. (Please DO NOT click [New Mutation] and re-enter the variant details into the top panel.)
2. Find the variant that you wish to record another incidence of and click "Edit".
3. Click on "New" at the top right hand corner of the middle panel (Centre submitting variant), select the name of the submitter for your centre and enter your methodology details. You only need to do this once for any given variant.
4. Next, click on "New" at the top right hand corner of the lower panel (Clinical Phenotype). If no phenotypic data is available or you do not wish to enter any clinical information then please ensure that you select "No phenotype information" from the "Details of index case" drop down menu.
5. Finally, click "Save" to add the record to the database.

Additional family (index case) seen at your centre

Additional entries should be made of the INDEX CASE ONLY from each new, apparently unrelated, individual carrying the variant:

1. Log-in and select [Mutations]
2. Find the variant that you wish to record another incidence of and click "Edit".
3. Navigate to your centre's entry in the middle panel. If the details here are correct, move to the bottom panel and enter phenotype information as steps 4 and 5 above.
4. If you have changed the detections methods, you will need to create another entry in the middle panel, using your centre submitter's name, with the new method details first: Follow steps 3 to 5 above.

After reading this, if you are still unsure about anything then please feel free to contact us.