As larger panels are used in genetic testing, there might be multiple different types of findings present in a single patient. Ideally, the genetic cause underlying patient’s disease is identified. We have improved our reporting to present the findings in a new, more informative way.
Positive findings are considered to be:
- pathogenic or likely pathogenic variants that are related to patient’s phenotype and are considered to explain the phenotype taking into account the inheritance model
- variants of uncertain significance (VUS) in a gene(s) that might be related to patient’s phenotype, but where the evidence is not strong enough to classify the variant as likely pathogenic
However, clinical significance of some findings remain unclear even after thorough analysis of all the information regarding the variant and current literature:
- Carrier status of a heterozygous variant of uncertain significance (VUS) for an autosomal recessive condition, which might be related to the patient’s phenotype but without second variant is not sufficient to explain the phenotype.
- Heterozygous variant of uncertain significance (VUS) for an autosomal dominant condition, which might be related to the patient’s phenotype
Additionally, the test can also reveal some additional findings, that are not related to the primary reason for performing the genetic test:
- Carrier status of a pathogenic/likely pathogenic variant in a gene, that is associated with autosomal recessive or X-linked inheritance, but which is not not related to the patient’s phenotype
- Heterozygous pathogenic/likely pathogenic variant for autosomal dominant disorder, which is not the primarily related to the patient’s phenotype
As large gene panels are being commonly used, they often result in identification of multiple variants of uncertain significance (VUS).
New report format
The new reporting layout is designed to organize the findings in a new, more informative way. The identified variants are re-organized to highlight the most important genetic findings more clearly, thus the information is divided into two sections:
- Main table(s): Variants that are thought to be main findings and are related to the patient’s phenotype will be reported in the Main variant table(s) with written statement about their clinical significance
- Additional findings table(s): Variants that are thought to be additional findings are reported in a separate variant table. This table will summarize the genomic position, HGVS annotation for the variant, ExAC allele count and number for the variant, OMIM, phenotypes related to that gene, in silico predictions (PolyPhen, SIFT, MutationTaster) and possible brief comments.
Variants that are reported in the Additional findings table will include:
- carrier status for a pathogenic/likely pathogenic variant for autosomal recessive or X-linked disorder, that is not related to the patient’s phenotype
- heterozygous pathogenic/likely pathogenic variant for autosomal dominant disorder (not related to the patient’s phenotype as given in the referral)
- carrier status for VUS variants for autosomal recessive or X-linked conditions