Abstract:
:Genetic testing has the potential to guide the prevention and treatment of disease in a variety of settings, and recent technical advances have greatly increased our ability to acquire large amounts of genetic data. The interpretation of this data remains challenging, as the clinical significance of genetic variation detected in the laboratory is not always clear. Although regulatory agencies and professional societies provide some guidance regarding the classification, reporting, and long-term follow-up of variants, few protocols for the implementation of these guidelines have been described. Because the primary aim of clinical testing is to provide results to inform medical management, a variant classification program that offers timely, accurate, confident and cost-effective interpretation of variants should be an integral component of the laboratory process. Here we describe the components of our laboratory's current variant classification program (VCP), based on 20 years of experience and over one million samples tested, using the BRCA1/2 genes as a model. Our VCP has lowered the percentage of tests in which one or more BRCA1/2 variants of uncertain significance (VUSs) are detected to 2.1% in the absence of a pathogenic mutation, demonstrating how the coordinated application of resources toward classification and reclassification significantly impacts the clinical utility of testing.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Eggington JM,Bowles KR,Moyes K,Manley S,Esterling L,Sizemore S,Rosenthal E,Theisen A,Saam J,Arnell C,Pruss D,Bennett J,Burbidge LA,Roa B,Wenstrup RJdoi
10.1111/cge.12315subject
Has Abstractpub_date
2014-09-01 00:00:00pages
229-37issue
3eissn
0009-9163issn
1399-0004journal_volume
86pub_type
杂志文章abstract::To create a diagnostic document describing the utilization of pre-implantation genetic testing (PGT) in the absence of monitoring and regulation. Retrospective cohort study of couples undergoing PGT between 2004 and 2007 in Lebanon. The clinical indications for 192 PGT cycles performed during the study period were gen...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12250
更新日期:2014-08-01 00:00:00
abstract::An extra G-positive band within the 9qh regions is reported as a new chromosome 9 variant. This variant may have been more prevalent than has hitherto been perceived. Due to its small size, this extra band might not be readily recognizable in routine G-staining. ...
journal_title:Clinical genetics
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doi:10.1111/j.1399-0004.1992.tb03654.x
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abstract::Usher syndrome has been historically categorized into one of three classical types based on the patient phenotype. However, the vestibular phenotype does not infallibly predict which Usher genes are mutated. Conversely, the Usher syndrome genotype is not sufficient to reliably predict vestibular function. Here we pres...
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doi:10.1111/cge.13868
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1987.tb02785.x
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abstract::Acetylation is one of the major routes in metabolism and detoxification of a large number of drugs, chemicals and carcinogens. Slow acetylators are said to be more susceptible to developing bladder cancer and because of investigations about tumor risk based on phenotyping procedures, it was our aim to study the distri...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1998.tb02753.x
更新日期:1998-05-01 00:00:00
abstract::Germline mutations of the STK11 gene mapped to chromosome 19p13.3 are responsible for Peutz Jeghers syndrome (PJS), a dominant disorder associated with characteristic gastrointestinal hamartomatous polyps and a predisposition to various cancers. We conducted a detailed investigation of germline STK11 alterations by pr...
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pub_type: 杂志文章
doi:10.1034/j.1399-0004.1999.560207.x
更新日期:1999-08-01 00:00:00
abstract::A 4-year-old Saudi female child with extreme failure to thrive, striking dysmorphic features, developmental delay, congenital hypoparathyroidism, UTI, seizures, chronic otitis media, chronic non-specific gastroenteritis and repeated life-threatening infections was followed from birth. She was the product of first-cous...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1992.tb03220.x
更新日期:1992-09-01 00:00:00
abstract::Reassessment of the cytogenetics of a patient previously karyotyped as del(16)(q22) demonstrates the presence of a balanced translocation, t(4;16)(q35;q22.1). This patient should not be included in any future comparison involving the clinical features of patients with deletions of the long arm of chromosome 16. ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1990.tb03614.x
更新日期:1990-12-01 00:00:00
abstract::The aim of the study was to determine any association of physical activity and Taq 1B polymorphism in the cholesteryl ester transfer protein gene on high-density lipoprotein (HDL) cholesterol. Five hundred and four subjects, 390 males and 114 females consisting of an equal number of age- and sex-matched healthy contro...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.0009-9163.2004.0237.x
更新日期:2004-05-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
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更新日期:1997-03-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/j.1399-0004.1992.tb03225.x
更新日期:1992-09-01 00:00:00
abstract::Two 1p36 contiguous gene deletion syndromes are known so far: the terminal 1p36 deletion syndrome and a 1p36 deletion syndrome with a critical region located more proximal at 1p36.23-1p36.22. We present even more proximally located overlapping deletions from seven individuals, with the smallest region of overlap compr...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13739
更新日期:2020-06-01 00:00:00
abstract::Two cases of previously unreported simultaneous presence of A and B postaxial polydactyly in two brothers out of 12 affected members of a kindred are reported. The findings are consistent with the hypothesis that in this family A and b types of postaxial polydactyly are caused by a single gene rather than by two diffe...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1980.tb02294.x
更新日期:1980-11-01 00:00:00
abstract::A sibship is reported of three generations of a Jordanian family of normal intelligence with a complex malformation of upper extremity, shoulder and thorax, which is combined with variously expressed congenital heart disease. The deformity consists of a flat glenoid fossa, a hypoplastic scapula, aplasia of the humerus...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1989.tb03374.x
更新日期:1989-12-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1992.tb03620.x
更新日期:1992-01-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
abstract::The increasing frequency with which the diagnosis of the 47,XXY karyotype is made requires more knowledge of the prognosis of this condition. We present four 47,XXY boys identified at birth and followed since then (Group I), and four 47,XXY boys diagnosed because of physical and/or emotional problems (Group II). Physi...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1981.tb01819.x
更新日期:1981-08-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12045
更新日期:2013-09-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1991.tb03011.x
更新日期:1991-03-01 00:00:00
abstract::The D/I (deletion, D, insertion, I) polymorphism of the angiotensin-converting enzyme (ACE) gene has been extensively studied for its association with a number of cardiovascular and other disease states. However, its potential association with differential clinical efficacy of ACE inhibitors (ACE-I) administered to pa...
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pub_type: 临床试验,杂志文章
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更新日期:2002-01-01 00:00:00
abstract::Non-syndromic deafness is a paradigm of genetic heterogeneity. More than 70 loci have been mapped, and 25 of the nuclear genes responsible for non-syndromic deafness have been identified. Autosomal-dominant genes are responsible for about 20% of the cases of hereditary non-syndromic deafness, with 16 different genes i...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
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更新日期:2002-07-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1990.tb03488.x
更新日期:1990-02-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
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更新日期:2006-01-01 00:00:00
abstract::We report the analysis of altogether 1050 suspected hereditary breast/ovarian cancer (HBOC) families, 524 fully screened for BRCA1/BRCA2 mutations and 526 tested only for the most common mutations. Of the 119 families with pathogenic mutations, 40 (33.6%) had the BRCA2 c.156_157insAlu rearrangement and 15 (12.6%) the ...
journal_title:Clinical genetics
pub_type: 杂志文章
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更新日期:2015-07-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1975.tb00320.x
更新日期:1975-03-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2021-01-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12371
更新日期:2015-03-01 00:00:00
abstract::436 index patients with major congenital urinary tract malformations, 385 with upper and 51 with lower urinary tract anomalies, were studied. A significant male sex predominance was noted in each group. No apparent correlation was found between parental age, birth order, birth weight and incidence of these malformatio...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1975.tb01952.x
更新日期:1975-07-01 00:00:00
abstract::Genetic and environmental factors have been implicated in the etiology of atopy and of serum IgE levels. In order to eliminate post-natal environmental influences we measured IgE in cord blood (CB-IgE) from a cohort of unselected, like-sexed twins. IgE determination was performed with a sensitive radioimmunoassay with...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1996.tb02384.x
更新日期:1996-11-01 00:00:00
abstract::Metacarpophalangeal pattern profile (MCPP) analysis was applied to patients with Pfeiffer and Chotzen syndromes, dominantly inherited types of acrocephalosyndactyly (ACS). A characteristic MCPP was obtained for the group. However, it did not discriminate between patients with Chotzen syndrome and those with Pfeiffer s...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1977.tb01316.x
更新日期:1977-04-01 00:00:00