## 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 cytogenetic 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 retrospective dataset displays microarray data submitted to dbGaP by cytogenetics labs of the ISCA Consortium, showing genomic regions found in patient who were referred for genetic testing for disorders such as mental retardation, developmental delay, autism and gross congenital malformation.

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. 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.

Many samples have multiple variants, not all of which are causative of the phenotype. The retrospective dataset was obtained from patients who were not asked for consent for release of their genetic information into a public database. To protect their privacy, the chromosome imbalances 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 oligo array CGH microarray from patients referred for cytogeneic testing due to clinical phenotypes. Samples were analyzed on a variety of microarray platforms, with a resolution of 20-75 kb, using pooled reference samples as control. Several consecutive probes were required before a region was determined to be either amplified or deleted. Where available, deletion endpoint uncertainty is described on the details page for each sample, 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 deletions and blue for duplications.

## Verification

Data were validated using a number of different methods, including variously, BAC aCGH, FISH, Karyotype and RT-PCR.

## Credits

Thanks to the ISCA Consortium, Christa Martin and Erin Baldwin of Emory University, David Ledbetter of the Geisinger Institute, Eric Thorland of Mayo Clinic and Swaroop Aradhya of GeneDx for samples and analysis. Thanks to Deanna Church and Justin Paschall of NCBI for consultation and integration into dbGaP and dbVar, and 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.