Gene Classification


A major challenge for diagnostic laboratories in the rapidly evolving genomics era is interpreting the gene classification (also known as clinical validity) of a gene-disease association, to ensure that a particular gene is indeed what is causing a patient’s disease.

Ambry scientists have recently published on our method for linking genes to diseases. This approach demonstrates the utility of establishing classification criteria of genes for both clinical diagnostic exome testing as well as for establishing the appropriate gene selection with the strongest gene-disease relationships for multi-gene panel tests (MGPT).

Ambry’s gene classification assessment criteria

Our gene classification criteria (clinical validity) assessment is based on a weighted scoring system guided by the ClinGen gene curation criteria, with points assigned to the relationship between one gene and one disease, based on existing literature and data. The cumulative score for a gene-disease relationship is based on scoring each line of supporting evidence; the sum of which classifies the gene-disease relationship as definitive, strong, moderate, or limited, or as a gene with no evidence for disease gene relationship.

Weighted lines of evidence

  • Number of unrelated patients
  • Publications with independent probands
  • Pathogenic variants
  • Gene function
  • Gene disruption
  • Model organism
  • Other supporting evidence, as applicable
Graphic showing the scoring method used with 0 equating to no-evidence and 15 to a definitive gene-disease relationship

Ambry’s application of our gene classification assessment criteria

Whether Exome or MGPT, Ambry’s high-quality products are developed and grounded in sound scientific evidence.

Scoring is a tool for evidence-based, quality genetic testing

Graphic showing the clinical validity of gene-disease associations with characterized genes having increased evidence over candidate genes

Clinical Diagnostic Exome (CDE)

Ambry uses our gene classification scoring scheme to define genes that are characterized versus those that are uncharacterized during exome analysis. Analysts use clinical validity scores to guide how we report individual results to patients and to identify new diagnoses in previously unsolved cases.

Gene selection for Multi-gene panel testing (MGPT)

Ambry uses our gene classification scoring scheme to select genes for a particular phenotype for MGPT. This results in the development of panels with genes that are more specific to a patient’s clinical presentation and reduces the burden of unclear clinical implications.


Peer-Reviewed Papers

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