Some conflicting ClinVar interpretations could be displayed with better information

[pnrobinson]

For instance, the following combination of interpretations means that we can probably discard the variant from furhter consideration, but the current Exomiser displays "conflicting interpretations", which necessitates opening the CLinVar page

Uncertain significance(1); Benign(3); Likely benign(2) 

It would be better to show something like

Conflicting interpretations: VUS(1);B(3);LB(2)

[julesjacobsen]

You're in luck - I'm working on updating some of the ClinVar stuff right now. Also, as luck would have it the ClinVar VCF file has the following INFO field

##INFO=<ID=CLNSIGCONF,Number=.,Type=String,Description="Conflicting clinical significance for this single variant; multiple values are separated by a vertical bar">

which appears when CLNSIG/CLNREVSTAT list conflicting interpretations e.g. (trimming out unwanted fields)

1       930200  1043045 G       A       .       .       CLNREVSTAT=criteria_provided,_conflicting_interpretations;CLNSIG=Conflicting_interpretations_of_pathogenicity;CLNSIGCONF=Uncertain_significance(1)|Likely_benign(1);
1       930201  2012623 C       T       .       .       CLNREVSTAT=criteria_provided,_single_submitter;CLNSIG=Uncertain_significance;
1       930203  972363  C       T       .       .       CLNREVSTAT=criteria_provided,_multiple_submitters,_no_conflicts;CLNSIG=Uncertain_significance

So, yes. This is a good idea and not so hard to achieve. I'd originally though this would require collating all this from the XML dump which would have led to a more negative response!

[julesjacobsen]

Added a new field and method Map<ClinSig, Integer> getConflictingInterpretationCounts() to the ClinVarData class and underlying protobuf representation in the new ClinVar MVStore (see #501). This allows display of the conflicting interpretation counts in the HTML e.g.

Previously: MISSENSE_VARIANT SNV 13-110855918-C-G [0/1] rs150182714 Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP3] ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (criteria provided, conflicting interpretations)

Updated: MISSENSE_VARIANT SNV 13-110855918-C-G [0/1] rs150182714 Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP3] ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (criteria provided, conflicting interpretations) (VUS:1, LB:3)