[EXTERNAL] [IMPROVEDX] genotypes/phenotype

Samuel, Rana Rana.Samuel at VA.GOV
Fri Apr 6 21:26:28 UTC 2018

There is another source of variance that needs to be considered first: If you send the same sample (split) to different labs - one lab's may report that a mutation is present while the other lab may report that there is no mutation, or that a different mutation is present. So one reason for the differing phenotype may be that the genotype is incorrect! 

We have a LONG way to go before we get to standardization and reproducibility of genetic test results between differing analytic platforms. Even among pathologists (the supposed-to-be experts on lab tests) there is very slow dissemination and even slower uptake, of the limits of analytic and clinical validity of these tests. At this time, the cottage industry of homegrown tests being marketed under the umbrella of 'precision medicine' is exploding, and unfortunately, the designated gatekeeper (the FDA) does not have the resources or the mandate to ensure rigorous proof of analytic and clinical validity, especially between competing systems/platforms ostensibly looking for the same genes.

See references attached above, especially the highlighted paragraph from the "Quality Assurance in Genetic testing" section on page 5 of the 2015 ASCO statement published in the JCO.

Great forum. The multidisciplinary input, especially from patient advocates, is exemplary.

Rana Samuel, MD, FCAP
Chief, Pathology and Laboratory Medicine Service (PALMS, 113)
Lead pathologist - VISN 2
VA western New York Healthcare System (VAWNYHS)
3495 Bailey Avenue, Buffalo, NY 14215
Ph:    716-862-8701
Fax:  716-862-7824
Rana.samuel at va.gov

-----Original Message-----
From: Robert Bell [mailto:0000000296e45ec4-dmarc-request at LIST.IMPROVEDIAGNOSIS.ORG] 
Sent: Friday, April 06, 2018 1:22 PM
Subject: [EXTERNAL] [IMPROVEDX] genotypes/phenotype

Dear all,

Following up on the genetic aspects of diagnosis with mutations, I am told that with the same mutation/genotype the phenotype can sometimes differ. I would welcome confirmation of this.

How do dIagnostic skills handle differing phenotypes with the same genotype? What contribution to error does that produce?

Rob Bell M.D.

Sent from my iPad

Moderator: David Meyers, Board Member, Society to Improve Diagnosis in Medicine

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