Clinical Utility of Reinterpreting Previously Reported Genomic Epilepsy Test Results for Pediatric Patients

Jeffrey A. Sorelle, Drew Michael Thodeson, Susan Arnold, Garrett Gotway, Jason Y Park

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Importance: Clinical genomic tests that examine the DNA sequence of large numbers of genes are commonly used in the diagnosis and management of epilepsy in pediatric patients. The permanence of genomic test result interpretations is not known. Objective: To investigate the value of reinterpreting previously reported genomic test results. Design, Setting, and Participants: This study retrospectively reviewed and reinterpreted genomic test results from July 1, 2012, to August 31, 2015, for pediatric patients who previously underwent genomic epilepsy testing at a single tertiary care pediatric health care facility. Reinterpretation of previously reported variants was conducted in May 2017. Main Outcomes and Measures: Patient reports from clinical genomic epilepsy tests were reviewed, and all reported genetic variants were reinterpreted using 2015 consensus standards and guidelines for interpreting hereditary genetic variants. Three classification tiers were used in the reinterpretation: pathogenic or likely pathogenic variant, variant of uncertain significance (VUS), or benign or likely benign variant. Results: A total of 309 patients had genomic epilepsy tests performed (mean [SD] age, 5.6 [0.8] years; 163 [52.8%] male), and 185 patients had a genetic variant reported. The reported variants resulted in 61 patients with and 124 patients without a genetic diagnosis (VUS variants only). On reinterpretation of all reported variants, 67 of the 185 patients (36.2%) had a change in variant classification. Of the 67 patients with a genetic variant change in interpretation, 21 (31.3%) experienced a change in diagnosis. During the 5 years of the study, 19 of 61 patients (31.1%) with a genetic diagnosis and 48 of 124 patients (38.7%) with undiagnosed conditions (VUS only) had their results reclassified. Review of genomic reports issued during the final 2 years of the study identified reclassification of variants in 4 of 16 patients (25.0%) with a pathogenic or likely pathogenic variant and 11 of 41 patients (26.8%) with a VUS. Conclusions and Relevance: The identified high rate of reinterpretation in this study suggests that interpretation of genomic test results has rapidly evolved during the past 5 years. These findings suggest that reinterpretation of genomic test results should be performed at least every 2 years..

Original languageEnglish (US)
JournalJAMA Pediatrics
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Epilepsy
Pediatrics
Health Facilities
Tertiary Healthcare
Outcome Assessment (Health Care)
Guidelines
Delivery of Health Care

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Clinical Utility of Reinterpreting Previously Reported Genomic Epilepsy Test Results for Pediatric Patients. / Sorelle, Jeffrey A.; Thodeson, Drew Michael; Arnold, Susan; Gotway, Garrett; Park, Jason Y.

In: JAMA Pediatrics, 01.01.2018.

Research output: Contribution to journalArticle

Sorelle, Jeffrey A. ; Thodeson, Drew Michael ; Arnold, Susan ; Gotway, Garrett ; Park, Jason Y. / Clinical Utility of Reinterpreting Previously Reported Genomic Epilepsy Test Results for Pediatric Patients. In: JAMA Pediatrics. 2018.
@article{8e7d3afd953041b297e837f099a13040,
title = "Clinical Utility of Reinterpreting Previously Reported Genomic Epilepsy Test Results for Pediatric Patients",
abstract = "Importance: Clinical genomic tests that examine the DNA sequence of large numbers of genes are commonly used in the diagnosis and management of epilepsy in pediatric patients. The permanence of genomic test result interpretations is not known. Objective: To investigate the value of reinterpreting previously reported genomic test results. Design, Setting, and Participants: This study retrospectively reviewed and reinterpreted genomic test results from July 1, 2012, to August 31, 2015, for pediatric patients who previously underwent genomic epilepsy testing at a single tertiary care pediatric health care facility. Reinterpretation of previously reported variants was conducted in May 2017. Main Outcomes and Measures: Patient reports from clinical genomic epilepsy tests were reviewed, and all reported genetic variants were reinterpreted using 2015 consensus standards and guidelines for interpreting hereditary genetic variants. Three classification tiers were used in the reinterpretation: pathogenic or likely pathogenic variant, variant of uncertain significance (VUS), or benign or likely benign variant. Results: A total of 309 patients had genomic epilepsy tests performed (mean [SD] age, 5.6 [0.8] years; 163 [52.8{\%}] male), and 185 patients had a genetic variant reported. The reported variants resulted in 61 patients with and 124 patients without a genetic diagnosis (VUS variants only). On reinterpretation of all reported variants, 67 of the 185 patients (36.2{\%}) had a change in variant classification. Of the 67 patients with a genetic variant change in interpretation, 21 (31.3{\%}) experienced a change in diagnosis. During the 5 years of the study, 19 of 61 patients (31.1{\%}) with a genetic diagnosis and 48 of 124 patients (38.7{\%}) with undiagnosed conditions (VUS only) had their results reclassified. Review of genomic reports issued during the final 2 years of the study identified reclassification of variants in 4 of 16 patients (25.0{\%}) with a pathogenic or likely pathogenic variant and 11 of 41 patients (26.8{\%}) with a VUS. Conclusions and Relevance: The identified high rate of reinterpretation in this study suggests that interpretation of genomic test results has rapidly evolved during the past 5 years. These findings suggest that reinterpretation of genomic test results should be performed at least every 2 years..",
author = "Sorelle, {Jeffrey A.} and Thodeson, {Drew Michael} and Susan Arnold and Garrett Gotway and Park, {Jason Y}",
year = "2018",
month = "1",
day = "1",
doi = "10.1001/jamapediatrics.2018.2302",
language = "English (US)",
journal = "JAMA Pediatrics",
issn = "2168-6203",
publisher = "American Medical Association",

}

TY - JOUR

T1 - Clinical Utility of Reinterpreting Previously Reported Genomic Epilepsy Test Results for Pediatric Patients

AU - Sorelle, Jeffrey A.

AU - Thodeson, Drew Michael

AU - Arnold, Susan

AU - Gotway, Garrett

AU - Park, Jason Y

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Importance: Clinical genomic tests that examine the DNA sequence of large numbers of genes are commonly used in the diagnosis and management of epilepsy in pediatric patients. The permanence of genomic test result interpretations is not known. Objective: To investigate the value of reinterpreting previously reported genomic test results. Design, Setting, and Participants: This study retrospectively reviewed and reinterpreted genomic test results from July 1, 2012, to August 31, 2015, for pediatric patients who previously underwent genomic epilepsy testing at a single tertiary care pediatric health care facility. Reinterpretation of previously reported variants was conducted in May 2017. Main Outcomes and Measures: Patient reports from clinical genomic epilepsy tests were reviewed, and all reported genetic variants were reinterpreted using 2015 consensus standards and guidelines for interpreting hereditary genetic variants. Three classification tiers were used in the reinterpretation: pathogenic or likely pathogenic variant, variant of uncertain significance (VUS), or benign or likely benign variant. Results: A total of 309 patients had genomic epilepsy tests performed (mean [SD] age, 5.6 [0.8] years; 163 [52.8%] male), and 185 patients had a genetic variant reported. The reported variants resulted in 61 patients with and 124 patients without a genetic diagnosis (VUS variants only). On reinterpretation of all reported variants, 67 of the 185 patients (36.2%) had a change in variant classification. Of the 67 patients with a genetic variant change in interpretation, 21 (31.3%) experienced a change in diagnosis. During the 5 years of the study, 19 of 61 patients (31.1%) with a genetic diagnosis and 48 of 124 patients (38.7%) with undiagnosed conditions (VUS only) had their results reclassified. Review of genomic reports issued during the final 2 years of the study identified reclassification of variants in 4 of 16 patients (25.0%) with a pathogenic or likely pathogenic variant and 11 of 41 patients (26.8%) with a VUS. Conclusions and Relevance: The identified high rate of reinterpretation in this study suggests that interpretation of genomic test results has rapidly evolved during the past 5 years. These findings suggest that reinterpretation of genomic test results should be performed at least every 2 years..

AB - Importance: Clinical genomic tests that examine the DNA sequence of large numbers of genes are commonly used in the diagnosis and management of epilepsy in pediatric patients. The permanence of genomic test result interpretations is not known. Objective: To investigate the value of reinterpreting previously reported genomic test results. Design, Setting, and Participants: This study retrospectively reviewed and reinterpreted genomic test results from July 1, 2012, to August 31, 2015, for pediatric patients who previously underwent genomic epilepsy testing at a single tertiary care pediatric health care facility. Reinterpretation of previously reported variants was conducted in May 2017. Main Outcomes and Measures: Patient reports from clinical genomic epilepsy tests were reviewed, and all reported genetic variants were reinterpreted using 2015 consensus standards and guidelines for interpreting hereditary genetic variants. Three classification tiers were used in the reinterpretation: pathogenic or likely pathogenic variant, variant of uncertain significance (VUS), or benign or likely benign variant. Results: A total of 309 patients had genomic epilepsy tests performed (mean [SD] age, 5.6 [0.8] years; 163 [52.8%] male), and 185 patients had a genetic variant reported. The reported variants resulted in 61 patients with and 124 patients without a genetic diagnosis (VUS variants only). On reinterpretation of all reported variants, 67 of the 185 patients (36.2%) had a change in variant classification. Of the 67 patients with a genetic variant change in interpretation, 21 (31.3%) experienced a change in diagnosis. During the 5 years of the study, 19 of 61 patients (31.1%) with a genetic diagnosis and 48 of 124 patients (38.7%) with undiagnosed conditions (VUS only) had their results reclassified. Review of genomic reports issued during the final 2 years of the study identified reclassification of variants in 4 of 16 patients (25.0%) with a pathogenic or likely pathogenic variant and 11 of 41 patients (26.8%) with a VUS. Conclusions and Relevance: The identified high rate of reinterpretation in this study suggests that interpretation of genomic test results has rapidly evolved during the past 5 years. These findings suggest that reinterpretation of genomic test results should be performed at least every 2 years..

UR - http://www.scopus.com/inward/record.url?scp=85056104035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056104035&partnerID=8YFLogxK

U2 - 10.1001/jamapediatrics.2018.2302

DO - 10.1001/jamapediatrics.2018.2302

M3 - Article

C2 - 30398534

AN - SCOPUS:85056104035

JO - JAMA Pediatrics

JF - JAMA Pediatrics

SN - 2168-6203

ER -