Measuring clinical utility in the context of genetic testing: a scoping review

Abstract We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for color vision deficiency (CVD). Deuteranopia affects 1 in 12 males and is inherited in an X-linked recessive manner. It is associated with variations in the OPN1LW (OMIM gene: 300822; OMIM disease: 303900) and OPN1MW (OMIM gene: 300821; OMIM disease: 303800) genes. Tritanopia has a prevalence of 1 in 10 000, is inherited in an autosomal dominant manner, and is related to variations in the OPN1SW (OMIM gene: 613522; OMIM disease: 190900) gene. Blue cone monochromatism has a prevalence of 1 in 100 000, is inherited in an X-linked recessive manner and is related to mutations in the OPN1LW (OMIM gene: 300822; OMIM disease: 303700) and OPN1MW (OMIM gene: 300821; OMIM disease: 303700) genes. Clinical diagnosis is based on clinical findings, ophthalmogical examination, family history, electroretingraphy, color vision testing and dark adaptometry. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

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The clinical utility of genetic testing of tissues from pregnancy losses

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/1471-0528.14229 ◽

2016 ◽

Vol 125 (7) ◽

pp. 867-873 ◽

Cited By ~ 2

Author(s):

CA Waterman ◽

P Batstone ◽

N Bown ◽

L Cresswell ◽

C Delmege ◽

...

Keyword(s):

Genetic Testing ◽

Clinical Utility

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Is There Any Clinical Utility to Genetic Testing for Patients With Congenital Heart Disease?

Seminars in Thoracic and Cardiovascular Surgery Pediatric Cardiac Surgery Annual ◽

10.1053/j.pcsu.2021.04.002 ◽

2021 ◽

Vol 24 ◽

pp. 26-29

Author(s):

Richard W. Kim

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Genetic Testing ◽

Clinical Utility ◽

Congenital Heart

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Genetic testing for Mendelian myopia

The EuroBiotech Journal ◽

10.24190/issn2564-615x/2017/s1.23 ◽

2017 ◽

Vol 1 (s1) ◽

pp. 74-76

Author(s):

Andi Abeshi ◽

Pamela Coppola ◽

Tommaso Beccari ◽

Munis Dundar ◽

Leonardo Colombo ◽

...

Keyword(s):

Risk Assessment ◽

Genetic Testing ◽

Clinical Utility ◽

Autosomal Recessive ◽

Autosomal Dominant ◽

Scientific Literature ◽

Genetic Test ◽

Clinical Findings ◽

Ophthalmological Examination ◽

Recessive Transmission

Abstract We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for Mendelian myopia (MM), a large and heterogeneous group of inherited refraction disorders. Variations in the SLC39A5, SCO2 and COL2A1 genes have an autosomal dominant transmission, whereas those in the LRPAP1, P3H2, LRP2 and SLITRK6 genes have autosomal recessive transmission. The prevalence of MM is currently unknown. Clinical diagnosis is based on clinical findings, family history, ophthalmological examination and other tests depending on complications. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

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The Potential Utility of Pharmacogenetic Testing in Psychiatry

Psychiatry Journal ◽

10.1155/2014/730956 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 12

Author(s):

Kathryn R. Gardner ◽

Francis X. Brennan ◽

Rachel Scott ◽

Jay Lombard

Keyword(s):

Genetic Testing ◽

Patient Outcomes ◽

Healthcare Costs ◽

Clinical Utility ◽

Psychiatric Patients ◽

Psychotropic Medications ◽

Pharmacogenetic Testing ◽

Wide Range ◽

Treatment Plans ◽

Varied Response

Over the last decade, pharmacogenetics has become increasingly significant to clinical practice. Psychiatric patients, in particular, may benefit from pharmacogenetic testing as many of the psychotropic medications prescribed in practice lead to varied response rates and a wide range of side effects. The use of pharmacogenetic testing can help tailor psychotropic treatment and inform personalized treatment plans with the highest likelihood of success. Recently, many studies have been published demonstrating improved patient outcomes and decreased healthcare costs for psychiatric patients who utilize genetic testing. This review will describe evidence supporting the clinical utility of genetic testing in psychiatry, present several case studies to demonstrate use in everyday practice, and explore current patient and clinician opinions of genetic testing.

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Clinical Utility of a Phenotype-Enhanced MYH7 -Specific Variant Classification Framework in Hypertrophic Cardiomyopathy Genetic Testing

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.120.003039 ◽

2020 ◽

Vol 13 (5) ◽

pp. 453-459

Author(s):

Connor L. Mattivi ◽

J. Martijn Bos ◽

Richard D. Bagnall ◽

Natalie Nowak ◽

John R. Giudicessi ◽

...

Keyword(s):

Genetic Testing ◽

Hypertrophic Cardiomyopathy ◽

Mayo Clinic ◽

Clinical Utility ◽

Similar Distribution ◽

Variant Classification ◽

Classification Framework ◽

Uncertain Significance ◽

Genetics And Genomics ◽

Independent Cohort

Background: Missense variants in the MYH7 -encoded MYH7 (beta myosin heavy chain 7) represent a leading cause of hypertrophic cardiomyopathy (HCM). MYH7 -specific American College of Medical Genetics and Genomics (ACMG) variant classification guidelines were released recently but have yet to be assessed independently. We set out to assess the performance of the MYH7 -specific ACMG guidelines and determine if the addition of phenotype-enhanced criteria (PE-ACMG) using the HCM Genotype Predictor Score can further reduce the burden of variants of uncertain significance (VUS). Methods: Re-assessment was performed on 70 MYH7 -variants in 121 unique patients from Mayo Clinic, and an independent cohort of 54 variants in 70 patients from Royal Prince Alfred Hospital (Australia). Qualifying variants were re-adjudicated using both standard ACMG and MYH7 -ACMG guidelines, and HCM Genotype Predictor Score was used to provide a validated measure of strength of clinical phenotype to be incorporated into the MYH7 -ACMG framework. Results: Among Mayo Clinic identified variants, 11/70 (16%) were classified as pathogenic (P), 10/70 (14%) as likely pathogenic, and 49/70 (70%) as a VUS. A similar distribution was seen in the Australian patients (12/54 [22%] P, 12/54 [22%] likely pathogenic, and 30/54 [56%] VUS; P =not significant). Application of the MYH7 -ACMG resulted in a nonsignificant reduction of the VUS burden in both cohorts from 49/70 to 39/70 (56%; P =0.1; Mayo Clinic) and from 30/54 to 20/54 (37%; P =0.1; Australia). Using the combined PE-MYH7-ACMG framework, the VUS decreased significantly from 49 to 27 ( P <0.001, Mayo Clinic) and from 30 to 16 ( P <0.001; Australia). Conclusions: Use of the MYH7 -specific guidelines alone failed to significantly decrease VUS burden in 2 independent cohorts. However, a significant reduction in VUS burden was observed after the addition of phenotypic criteria. Using a patient’s strength of sarcomeric HCM phenotype for variant adjudication can increase significantly the clinical utility of genetic testing for patients with HCM.

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Expanded yield of multiplex panel testing in fully accrued prospective trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1525 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1525-1525

Author(s):

Gregory Idos ◽

Allison W. Kurian ◽

Charite Nicolette Ricker ◽

Duveen Sturgeon ◽

Julie Culver ◽

...

Keyword(s):

Risk Assessment ◽

Genetic Testing ◽

Cancer Risk ◽

Clinical Utility ◽

Diagnostic Yield ◽

Pathogenic Mutation ◽

Gene Panel ◽

Cancer Risk Assessment ◽

Panel Testing ◽

Gene Panel Testing

1525 Background: Genetic testing is a powerful tool for stratifying cancer risk. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. However, the diagnostic yield and clinical utility of panels remain to be further delineated. Methods: A report of a fully accrued trial (N = 2000) of patients undergoing cancer-risk assessment. Patients were enrolled in a multicenter prospective cohort study where diagnostic yield and off-target mutation detection was evaluated of a 25 gene MGP comprised of APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were enrolled if they met standard testing guidelines or were predicted to have a ≥2.5% mutation probability by validated models. Differential diagnoses (DDx) were generated after expert clinical genetics assessment, formulating up to 8 inherited cancer syndromes ranked by estimated likelihood. Results: 1998/2000 patients had reported MGP test results. Women constituted 81% of the sample, and 40% were Hispanic; 241 tested positive for at least 1 pathogenic mutation (12.1%) and 689 (34.5%) patients carried at least 1 variant of uncertain significance. The most frequently identified mutations were in BRCA1 (17%, n = 41), BRCA2 (15%, n = 36), APC (8%, n = 19), CHEK2 (7%, n = 17), ATM (7%, n = 16). 39 patients (16%) had at least 1 pathogenic mutation in a mismatch repair (MMR) gene ( MLH1, n = 10; MSH2, n = 10; MSH6, n = 8; PMS2, n = 11). 43 individuals (18%) had MUTYH mutations – 41 were monoallelic. Among 19 patients who had mutations in APC – 16 were APC I1307K. Only 65% (n = 159) of PV results were included in the DDx, with 35% (n = 86) of mutations not clinically suspected. Conclusions: In a diverse cohort, multiplex panel use increased genetic testing yield substantially: 35% carried pathogenic mutations in unsuspected genes, suggesting a significant contribution of expanded multiplex testing to clinical cancer risk assessment. The identification of off-target mutations broadens our understanding of cancer risk and genotype-phenotype correlations. Follow-up is ongoing to assess the clinical utility of multiplex gene panel testing. Clinical trial information: NCT02324062.

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