ACMG classification improved on VarSome Clinical Version 7

The Saphetor Portal has been updated to version 7 as of February 2nd 2019 under the new name VarSome Clinical. There are many changes since version 6, and this release brings our clinical platform up to date with the features, databases and classification visible in the free VarSome.com. Our clinical platform has been on the market since 2015 and is already being used by dozens of institutional clients, such as diagnostic laboratories, hospitals, and universities from countries all over the world.

This recent update features, among other improvements, the following changes in the process of annotation using the ACMG implementation:

ACMG Annotation

VarSome Clinical's ACMG annotation methodology is constantly under review following feedback from 100.000-strong VarSome community and our own clinical advisors. This release brings our clinical platform up to date and in sync with the annotations of the free VarSome.com. Key changes include:

• The functional annotation of variants has been improved, it now takes the full impact to the protein transcript into account.

• A new “splice junction loss” coding impact is used in rule PM4.

• Rules PM1 & PM4 are now mutually exclusive.

• Rules BP4 & BP7 are now mutually exclusive.

• Splice-site prediction from the scSNV database is used in rules BP4/PP3.

• ACMG annotation is no longer provided for variants that are outside any transcript.

• Rules PS1 & PM5 now perform a full ACMG re-annotation to confirm the pathogenicity of variants reported by ClinVar, UniProt or the VarSome community.

• Multiple minor fixes & improvements.