Genomic evidence score · BEGINNER LESSON
HI score
In ClinGen dosage sensitivity curation, the HI score is a numerical rating of how much evidence supports haploinsufficiency as a disease mechanism for a gene or genomic region. Haploinsufficiency means that losing one functional copy of a gene is enough to contribute to disease.
What it is and what is measured
The HI score is part of ClinGen’s dosage sensitivity curation. It measures the strength of evidence that haploinsufficiency, or HI, is a valid disease mechanism for a gene or genomic region. In plain terms, curators ask whether having only one working copy, instead of two, is linked to disease. The score is numerical: 3 means sufficient evidence, 2 means emerging evidence, 1 means little evidence, and 0 means no evidence for HI as a disease mechanism.
How the score is used
ClinGen evaluates genes and genomic regions seen in tests such as cytogenomic array testing, exome sequencing, and genome sequencing. If a deletion fully includes a gene or region with an HI score of 3, that deletion may be classified as pathogenic without needing extra supporting evidence under the ACMG and ClinGen technical standards for constitutional copy number variant, or CNV, analysis. CNV means a change in the number of copies of DNA.
How the evidence works
The score is based on curation, which means careful review of published and other available evidence. A high HI score does not mean every loss of that gene will cause the same result; it means the evidence is strong enough to support HI as a disease mechanism. ClinGen also assigns separate scores for triplosensitivity, or TS, which is a different question: whether having an extra copy contributes to disease.
Limitations
The score is evidence-based, so it depends on what is known at the time of curation. Lower scores can reflect limited or missing evidence, not proof that a gene is safe or irrelevant. The source also notes that TS evidence is often limited for small copy-number gains because information about orientation and exact genomic location is not always available, and because whole-gene duplications are uncommon. For HI, the score is still a curation result, not a direct measurement of a patient’s outcome.
SEE THE IDEA
How a ClinGen HI score is assigned
The object being evaluated
Curators examine data from tests and reports
Higher numbers mean stronger support for haploinsufficiency as a disease mechanism
A deletion including a gene with HI score 3 may support a pathogenic classification
Evidence is reviewed for a gene or region, then summarized as an HI score that can inform copy-number variant interpretation.
The HI score turns collected evidence into a graded statement about whether loss of one copy can cause disease.
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Sources and further reading
This general lesson was generated from public source material. It explains a concept; it does not interpret a private paper or provide medical advice.