Release

Notes
Alamut Visual Plus version 1.6.1 July 12, 2022

We are constantly working to enhance our variant annotation features while improving the
user-friendly experience of Alamut Visual Plus for you!

NEW

BRCA Exchange
• The clinical significance of variants in the BRCA1 and BRCA2 genes according to the
BRCA Exchange catalog (https://brcaexchange.org) is now included in a separate
track and in the final report.

gnomAD FAF (Filtering Allele Frequency)

• FAF scores (https://gnomad.broadinstitute.org/help/faf) are now displayed in the
tooltip of the allele frequency track, in the variant panel, and in the final report.

Sharing Local Databases

• Local Variant Databases and Private Annotations Databases can now be flagged as
“shared”.
• Read and Write performances have been improved to reduce possible latency issues
in a shared environment.

UPDATED
• From the transcript track, we can now see the number of selected nucleotides in
the tooltip when a genomic sequence is highlighted.
• The user is now asked to confirm if they would like to delete a Local Variant
Database.
• Private annotations are now automatically mapped between assemblies.
• In the Variant Panel, in the Occurrences sub-tab, it is now possible to filter the
existing occurrences list thanks to the addition of a dedicated search field.
• When importing variants in a Local Variant Database (for example when using .mut files from
Alamut Visual), multiple options can now be applied to manage the existing variants:
o Do not import already existing variants – conflicting variants will be ignored during the import
process.
o Overwrite variants if already exist – in case of conflicts, the variants to import will replace the
existing ones.
o Update existing variants and add history entry – variants get normally imported, a new entry will be
added to the variant history to track the updates.
• Sequence lookup performances have been sped up for the ‘Focus on’ feature.
• The LRG mapping mechanism between assemblies has been enhanced for reverse
genes.
• Fixing variant annotation from external catalogs for duplications
The new release of Alamut Visual Plus version 1.6.1 can be downloaded from the Extranet
from Tuesday 12th of July 2022, onwards.

Please consult our regularly updated User Manual to find out more about the new and
updated features in the current Release Note.

If you have any questions, feel free to contact our team at [email protected]

SOPHiA GENETICS products are for Research Use Only and not for use in diagnostic procedures unless specified
otherwise. Information about products which may or may not be available in different countries and if
applicable, may or may not have received approval or market clearance by a governmental regulatory body for
different indications for use. Please contact us at [email protected] to obtain the appropriate
product information for your country of residence.

Previous versions

Alamut Visual Plus version 1.5 March 15, 2022

We are constantly working to enhance our variant annotation features while improving the
user-friendly experience of Alamut Visual Plus for you!

NEW

CADD Scoring
• Alamut Visual Plus now shows missense variant scores from the Combined
Annotation Dependent Depletion (CADD) database – a community-developed tool
that scores the deleteriousness of SNVs.

Variant Interactive Filtering

• This new feature to Alamut Visual Plus allows the user to dynamically filter for
their variant of interest, based on criteria such as assembly, chromosome, gene,
transcript, ACMG evidences, and gNomen. The filtered variants are displayed as a
table below the tracks and are automatically refreshed while moving through the
genome viewer.

UPDATED

With this release, the following features have been updated:

Improved Sanger Sequencing Viewing

• It is now possible to align your Sanger Sequencing track to a genomic region on
Alamut Visual Plus – enabling mapping to multiple exons or an intronic area.

Improved Occurrence Management with Variants

 • We have improved the comments structure to allow a comment to be associated
with a variant or an individual occurrence. This change also ensures historical
comments from Alamut Visual are kept in Alamut Visual Plus.

API Improvements
• It is now possible to perform multiple searches and to open multiple variants
simultaneously through the Alamut Visual Plus API.

Improved Private Annotation Database Import to Alamut Visual Plus

• The mechanism for Private Annotation Database import to Alamut Visual Plus from
Alamut Visual has been updated to allow a more seamless and complete transfer of
historical variant data.

Improved Private Annotation Visualization

• The private annotation track on the genome viewer has been improved to allow
visualization of variants across the whole genome – viewed as annotations on the
track.

ACMG Display Improvements

• The ACMG evidence display has been updated to consider user-defined evidence
selections as well as automatically computed evidence.

Focus On - Approximate Matching

• It is now possible to perform approximate matching focus-on requests.
Alamut Visual Plus version 1.4 December 7, 2021

We are constantly working to enhance our variant annotation features while improving the
user-friendly experience of Alamut Visual Plus for you!

NEW

Two databases: PolyPhen-2 and BRIDGES

These curated databases will allow improved classification and annotation of variants.

▪ PolyPhen–2 (Polymorphism Phenotyping v2) interprets and scores deleterious SNVs

in the whole human exome sequence space (WHESS). It will be displayed in
“Missense predictions” as a new line, and in the final report. This database is
hosted by Harvard Medical School:
http://genetics.bwh.harvard.edu/pph2/dbsearch.shtml

▪ The BRIDGES database shows association scores of rare variants in 34 putative

breast cancer genes. BRIDGES (Breast Cancer Risk after Diagnostic Gene
Sequencing) investigated over 20,000 breast cancer cases, 20,000 controls, and
10,000 multiple-case families to identify variants that represent a high risk of
breast cancer: https://bridges-research.eu/ - BRIDGES will be shown as an icon in
“Gene view”.

UPDATED

With this release, the following features have been updated:

▪ The new /annotate endpoint of the API can gather annotations relating to a variant
and return the result in the JSON format.

▪ It is now possible to redefine the database where variants will be saved by default.

▪ New navigation options have been added to look for deletion and insertions (in
addition to substitutions) within BAM files.

▪ It is now possible to look for strings of nucleotides in Locus Reference Genomic

(LRG) reference sequences.

▪ The transcript selection dialog now always displays the name of the Assembly.

▪ ACMG evidence has been added to the “Variant History” tab.

Alamut Visual Plus version 1.3 September 28, 2021

We are constantly working to enhance our variant annotation features while improving the
user-friendly experience of Alamut Visual Plus for you!

NEW
Generic profiles
This functionality allows the users from the same lab to standardize their variant
interpretation workflows by using defined user profiles. Some of the shared settings
include:
▪ BAM/CRAM files visualization settings
▪ Splicing settings
▪ Private annotation database
▪ Local variant database
▪ Preferred gene
▪ Preferred transcript

Extended list of transcripts

When available, the “Transcript selection” tab allows the display of up to four versions of
one transcript.

Zoom-in/Zoom-out options
Keyboard options allow zoom-in and zoom-out functionality.

UPDATED

▪ The final report now includes:

o Nucleotide conservation score for intronic regions
o Amino acid conservation score
o The physicochemical distance interpretation related to GranthamDist
o The frameshift variants description
o The chromosome ID related to gDNA

▪ The “Splicing tab” has been updated with:

o Zoom-in/zoom-out options to allow better visualization of the splicing
impact
o A default flanking region of 200bp (with the option to manually adjust the
region via the “Splicing predictions options” tab) for report generation.

▪ Opening of BAM files:

o The pop-up requesting to open a BAM file when switching from one gene to
another is disabled.
o The option to “Automatically load BAM files” in the “Misc” tab automatically
opens BAM files when opening a new gene in a new tab.
o The pop-up requesting upload of the VCF linked to the BAM file remains.

▪ For the “Variant Panel”, the option to “Ask for confirmation before saving variants”
is available in the “Misc” tab, and the pop-up requesting the confirm to save the
variant no longer exists.

▪ The pNomen nomenclature for Delins is updated.

 ▪ The variant coordinates will be automatically mapped from one assembly to the
next one, when the user decides to use a new one.

▪ The “GoTo” bar enables to search for the continuous gene and c. coordinate
columns pasted from an excel file (e.g. MLH1:c.12 or MLH1:12).

Alamut Visual Plus version 1.2 June 29, 2021

NEW

OMIM® database integration

The mode of inheritance and phenotype available from the Online Mendelian Inheritance in
Manâ (OMIM) are now included in the final report. [OMIM version 2021-05-
04, https://www.omim.org]

MANE transcripts implementation

A tag has been added in the “Transcript Selection” tab, interface, and “Report” to
distinguish those transcripts whose classification is based on the Matched Annotation
between NCBI and EBI (MANE). [MANE version
0.93, https://www.ncbi.nlm.nih.gov/refseq/MANE/]
pLI / LOEUF scores
The following gnomAD predicted scores at the gene level are now shown:
▪ the probability of loss-of-function intolerance (pLI)
[version 2.1.1, https://gnomad.broadinstitute.org/downloads]
▪ the loss-of-function observed/expected upper bound fraction (LOEUF).
[version 2.1.1, https://gnomad.broadinstitute.org/downloads]

The variant report from Sanger track — export option

Full-annotation variant report from the Sanger track can now be exported.
The private annotation track — import option
The import of text format in the private annotation track is now available.

UPDATED

With this release, the following features have been updated:

▪ When available, the total frequencies from gnomAD are now displayed
for exomes and genomes.

▪ The imported Sanger sequence can now be automatically aligned.

▪ In the Sanger track, users can now view only the sequence of the forward
strand as the reference. The reference sequence can be hidden when several
Sanger files are loaded simultaneously.
▪ The forward strand from Sanger sequence is now shown with a blue
background, and the reverse strand is shown with a green background.

▪ Already existing local variant databases can be imported and shared

between multiple users.
▪ The search bar now allows users to copy a list of variants, which appear in a
pop-up window and allow the investigation of different variants.
▪ It is now possible to enter a cDNA coordinate without c. to search for a
position.
 ▪ The option to remove the parentheses from the protein nomenclature now
exists.

▪ When searching for a nucleic sequence in the “Focus On” tab, the reverse
option is now available. The “focus on” allows simultaneous working on the
main screen.

▪ Former issues with the missing predictions from Polyphen are fixed, and the
predictions are now available.

▪ SIFT missense predictions are updated to version 6.2.0.

▪ Genesplicer and SSF scores display issues are now fixed.

▪ BAM reads are now displayed after the private annotation track.
▪ In the BAM options, “Show Clipped Bases” function is now shown directly in
the menu under “Show All Bases.”
▪ The transcript names are now shown in full in the “Transcript Tab”
selection.

▪ The date of the variant creation is now added to the “Variant Exporter.”

▪ From the “Variant Exporter” window, it is now possible to select/unselect

values for each filter.

▪ Linkouts to external database are now added in the top of the interface and
are directly accessible

Alamut Visual Plus version 1.1 April 27, 2021

NEW

Application Programming Interface (API)

Alamut Visual Plus now integrates API that enables access of the users’ external tools to be
easily reached through the search bar feature.

Private Annotations Display

Users now have the option to manually select DNA sequences and automatically import
them through a new dedicated track (e.g., sequence-based annotations including PCR
primers, probes, etc.).

Data Server for North America

With this release, users can benefit from a new data server, enabling faster data
visualization.

UPDATED

With this release, the following features have been updated:

▪ ACMG evidence description is included in “final report”

▪ Full display of genes is now possible in “chromosome

view”
 ▪ Splicing and missense scores are added in “variant
exporter” tab Updated design of “settings” window with improved
view configuration Font size of “variant panel” is increased

▪ Installation of Alamut Visual Plus is available from a shared

folder

▪ Proxy and low connectivity issues are sorted