## Description

NOTE:
While the ISCA data are open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal medical questions.

UCSC presents these data for use by qualified professionals, and even such professionals should use caution in interpreting the significance of information found here. No single data point should be taken at face value and such data should always be used in conjunction with as much corroborating data as possible. No treatment protocols should be developed or patient advice given on the basis of these data without careful consideration of all possible sources of information.

No attempt to identify individual patients should be undertaken. No one is authorized to attempt to identify patients by any means.

The International Standards for Cytogenomic Arrays (ISCA) Consortium is group of clinical cytogenetics and molecular genetics laboratories that has been organized to improve the quality of patient care in clinical genetic testing using new molecular cytogenetic technologies. These technologies include array comparative genomic hybridization (aCGH) and quantitative SNP analysis by microarrays or bead chips. Membership in the ISCA Consortium is open to all individuals and laboratories involved in clinical array testing who are committed to free data sharing and to participation in a process to develop evidence-based standards and guidelines to improve patient care.

The ISCA dataset displays clinical microarray data submitted to dbGaP/dbVar at NCBI by ISCA Consortium member laboratories. This track shows copy number variants (CNVs) found in patients referred for genetic testing for indications such as intellectual disability, developmental delay, autism and congenital anomalies.

The CNVs in this study have been reviewed for their clinical significance by the submitting ISCS laboratory. Some of the deletions and duplications reported in this track have been identified as causative for the phenotype by clinical cytogeneticists at those locations, and to the best of their knowledge represent the cause of the reported phenotype. However, it should be noted that phenotype information is often vague and imprecise and should be used with caution. While all samples were submitted because of a phenotype in a patient, only 15% of patients had variants determined to be causal, and most patients will have additional variants that are not causal.

CNVs are labeled as: Pathogenic, Uncertain: Likely Pathogenic, Uncertain, Uncertain: Likely Benign and Benign. The user should be aware that some of the data were submitted using a 3-class system, with the two "Likely" categories omitted.

Many samples have multiple variants, not all of which are causative of the phenotype. The CNVs in these samples have been decoupled, so it is not possible to connect multiple imbalances as coming from a single patient. It is therefore not possible to identify individuals via their genotype.

## Methods and Color Convention

The samples were analyzed by arrays from patients referred for cytogeneic testing due to clinical phenotypes. Samples were analyzed on with a probe spacing of 20-75 kb. The minimum CNV breakpoints are shown; if available, the maximum CNV breakpoints are provided in the details page,but is not shown graphically on the Browser image.

Data were submitted to dbGaP at NCBI and thence decoupled as described into dbVar for unrestricted release.

The entries are colored red for loss and blue for gain.

## Verification

Most data were validated by the submitting laboratory using various methods, including FISH, G-banded karyotype, MLPA and qPCR.

## Credits

Thanks to the ISCA Consortium, to Viren Patel at Emory University for technical coordination with ISCA on track details, to Deanna Church and Justin Paschall at NCBI for consultation and integration into dbGaP and dbVar, and to Angie Hinrichs and Robert Kuhn at UCSC for engineering.

## References

Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010 May 14;86(5):749-64.

Kaminsky EB, Kaul V, Paschall J, Church DM, Bunke B, Kunig D, Moreno-De-Luca D, Moreno-De-Luca A, Mulle JG, Warren ST et al. An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med. 2011 Sep;13(9):777-84.