Archives

22 Dec 2021

deficiency of mfsd7c results in microcephaly associated vasculopathy in fowler syndrome

Several missense mutations in the orphan transporter FLVCR2 have been reported in Fowler syndrome. Affected subjects exhibit signs of severe neurological defects. We identified the mouse ortholog Mfsd7c as a gene expressed in the blood-brain barrier. Here, we report the characterizations of Mfsd7c-KO mice and compare these characterizations to phenotypic findings in humans with biallelic… View Article
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22 Dec 2021

genotype phenotype associations in a large prph2 related retinopathy cohort

Molecular variant interpretation lacks disease gene‐specific cohorts for determining variant enrichment in disease versus healthy populations. To address the molecular etiology of retinal degeneration, specifically the PRPH2‐related retinopathies, we reviewed genotype and phenotype information obtained from 187 eyeGENE® participants from 161 families. Clinical details were provided by referring clinicians participating in the eyeGENE® Network. The… View Article
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22 Dec 2021

Data sharing to improve concordance in variant interpretation across laboratories results from the canadian open genetics repository

Accurate variant interpretation is essential for the benefits of clinical genetic testing to be realized. In variant interpretation, multiple lines of evidence are considered to evaluate a variant’s pathogenicity. Despite guidelines from the American College of Medical Genetics and Genomics (ACMG) and the Association of Molecular Pathology (AMP), discordant variant classifications exist between laboratories. Data… View Article
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20 Dec 2021

Rare Disease Discovery

Genoox reveals loss of Glycine Transporter 1 Causes a Subtype of Glycine Encephalopathy with Arthrogryposis and Mildly Elevated Cerebrospinal Fluid Glycine The Genoox sophisticated interpretation engine provides both automatic annotation and classification of variants, as well as advanced sample comparison and the ability to analyze families and examine different inheritance models, providing rapid clinical answers… View Article
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20 Dec 2021

NGS Validation

Comparing exome performance and Sanger-sequencing in the clinical setting Clinical uses of Next Generation Sequencing (NGS) are continually expanding as the cost of the technology falls while clinical utility increases at a rapid rate., What was once a “last resort” technique for exceptional cases in which a molecular diagnosis could not be achieved by standards… View Article
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20 Dec 2021

benchmarking an automated variant classification engine avce algorithm using clinvar

Results of a Time-Capsule Experiment The Genoox aVCE was ‘trained’ on the ClinVar database (version 30-06-17). Variants with Reference/Submission ClinVar (RCV/SCV) creation dates before and after 01-07-16 were marked as ‘Train’ and ‘Test,’ respectively. When compared against ClinVar submissions from clinical laboratories and high-certainty entries, the proprietary aVCE classified clinically ‘actionable’ (P/LP) and ‘non-actionable’ (VUS/LB/B)… View Article
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20 Dec 2021

a novel approach for structural variant calling

Combining Data from Whole Genome Next-generation Sequencing and Optical Mapping A novel joint pipeline integrating NGS raw data with optical mapping provided SV calls characterized by precise breakpoint positions and low false-positive rates, suggesting the advanced graph structure could have considerable utility in clinical practice. American Society of Human Genetics 2018 Annual Meeting October 16–20,… View Article
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20 Dec 2021

using artificial intelligence for implementing new recommendations of the pvs1 loss of function criterion

The aiVCE algorithm demonstrated excellent concordance with the ClinGen SVI Workgroup results. Further, the 5 variants demonstrating discordant classification strength illustrate an advantage of using an AI-based tool, as the identification of these variants as P were in agreement with the new ClinGen SVI Workgroup recommendations. Implementation of new recommendations for more accurate interpretation of… View Article
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20 Dec 2021

reinterpretation of sequence variants using artificial intelligence

Evaluating Genoox AI Engine as a Tool For Performing Variant Reinterpretation These benchmarking results demonstrate the aiVCE’s ability to classify variants at a high rate of concordance with expert curation. The high level of agreement with challenging variants, such as those in the Discordant Dataset, makes the aiVCE ideal to expedite reinterpretation of variants accumulated… View Article
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20 Dec 2021

implementation of gene specific clingen variant classification recommendations using artificial intelligence

Frequency Thresholds The 2015 ACMG/AMP sequence variant interpretation guidelines provided a framework for classifying variants based on several benign and pathogenic evidence criteria. Recently, ClinGen has introduced several expert gene/disease panels to establish more specific classification recommendations. We hypothesized that artificial intelligence (AI)-based algorithms that are focused on implementation of gene-specific recommendations may aid in… View Article
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