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WGLab / InterVar

A bioinformatics software tool for clinical interpretation of genetic variants by the 2015 ACMG-AMP guideline
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InterVar often underestimate the pathogenecity of a variant. #61

Open lincj1994 opened 3 years ago

lincj1994 commented 3 years ago

Hi, I've run InterVar on a testing data. The variant below was identified as likely pathogenic:

chr17 41244106 41244106 C - BRCA1 exonic frameshift deletion clinvar:Pathogenic InterVar: Likely pathogenic PVS1=1 PS=[0, 0, 0, 0, 0] PM=[0, 1, 0, 0, 0, 0, 0] PP=[0, 0, 0, 0, 0, 0] BA1=0 BS=[0, 0, 0, 0, 0] BP=[0, 0, 0, 0, 0, 0, 0, 0]

However, it was classified as pathogenic by ClinVar and PathoMAN (PVS1=1, PS3=1, PM2=1). So I strongly suggest to establish a database with validated genetic variants that are known to affect the function of genes or gene products.

quanliustc commented 3 years ago

Thanks for the suggestion, Without PS3, that could underestimate the clinical significance, as PS3 need well-established in vitro or in vivo functional studies to support,currently we have a PS3 database, but did not release it.

lincj1994 commented 3 years ago

Thanks for the suggestion, Without PS3, that could underestimate the clinical significance, as PS3 need well-established in vitro or in vivo functional studies to support,currently we have a PS3 database, but did not release it.

Thanks for your reply! Looking forward to the update of InterVar. I just expect a high corcondance between Clinvar and InterVar, at least in those Clinvar-annotated pathogenic or likely pathogenic variants. Btw, will the PS3 database be released in the coming updated InterVar?

lincj1994 commented 3 years ago

Thanks for the suggestion, Without PS3, that could underestimate the clinical significance, as PS3 need well-established in vitro or in vivo functional studies to support,currently we have a PS3 database, but did not release it.

Dr. Li, I think it should be assigned as PP5 by InterVar as well since it was classified as pathogenic by clinvar in this case. Why PP5 not assigned? Thank you . Lin.