ArticleHuman mutation2013
Large numbers of genetic variants considered to be pathogenic are common in asymptomatic individuals.
Article in Human mutation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- International policies guiding the selection, analysis, and clinical management of secondary findings from genomic sequencing: A systematic review.American journal of human genetics · 2024Pooled it
- Evidence for penetrance in patients without a family history of disease: a systematic review.European journal of human genetics : EJHG · 2020Pooled it
- Predicting Functional Effects of Synonymous Variants: A Systematic Review and Perspectives.Frontiers in genetics · 2019Pooled it
- The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial.Annals of internal medicine · 2017Trial
- Assessing the Clinical Relevance ofCurrent oncology (Toronto, Ont.) · 2026Article
- Population-scale genomic screening reveals high frequency of actionable secondary findings in Chinese newborns.NPJ genomic medicine · 2026Article
- Extracting and calibrating evidence of variant pathogenicity from population biobank data.American journal of human genetics · 2025Article
- A genotype-first approach identifies high incidence of NF1 pathogenic variants with distinct disease associations.Nature communications · 2025Article
- Variant Effect Prediction in the Age of Machine Learning.Cold Spring Harbor perspectives in biology · 2024Review
- Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity.Genome medicine · 2023Article
- ClinVar and HGMD genomic variant classification accuracy has improved over time, as measured by implied disease burden.Genome medicine · 2023Article
- Estimating clinical risk in gene regions from population sequencing cohort data.American journal of human genetics · 2023Article
- Modeling ofKidney international reports · 2023Article
- Estimating clinical risk in gene regions from population sequencing cohort data.medRxiv : the preprint server for health sciences · 2023Article
- Clinical exome-based panel testing for medically actionable secondary findings in a cohort of 383 Italian participants.Frontiers in genetics · 2022Article
- Rare variants discovery by extensive whole-genome sequencing of the Han Chinese population in Taiwan: Applications to cardiovascular medicine.Journal of advanced research · 2021Article
- A pipeline-friendly software tool for genome diagnostics to prioritize genes by matching patient symptoms to literature.Advanced genetics (Hoboken, N.J.) · 2020Article
- Reduced penetrance of pathogenic ACMG variants in a deeply phenotyped cohort study and evaluation of ClinVar classification over time.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- Variability in Gene Expression is Associated with Incomplete Penetrance in Inherited Eye Disorders.Genes · 2020Article
- Actionable Exomic Secondary Findings in 280 Lebanese Participants.Frontiers in genetics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
It is now affordable to order clinically interpreted whole-genome sequence reports from clinical laboratories. One major component of these reports is derived from the knowledge base of previously identified pathogenic variants, including research articles, locus-specific, and other databases. While over 150,000 such pathogenic variants have been identified, many of these were originally discovered in small cohort studies of affected individuals, so their applicability to asymptomatic populations is unclear. We analyzed the prevalence of a large set of pathogenic variants from the medical and scientific literature in a large set of asymptomatic individuals (N = 1,092) and found 8.5% of these pathogenic variants in at least one individual. In the average individual in the 1000 Genomes Project, previously identified pathogenic variants occur on average 294 times (σ = 25.5) in homozygous form and 942 times (σ = 68.2) in heterozygous form. We also find that many of these pathogenic variants are frequently occurring: there are 3,744 variants with minor allele frequency (MAF) ≥ 0.01 (4.6%) and 2,837 variants with MAF ≥ 0.05 (3.5%). This indicates that many of these variants may be erroneous findings or have lower penetrance than previously expected.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.