蛋白截断变异(protein-truncating variant,PTV)通过引入终止密码子,移码突变或剪接位点,破坏蛋白编码基因[1]。蛋白截断变异的研究对于人类进化(human evolution),基因功能(gene function),疾病相关变异(disease-related variants)和疾病患者变异的临床解读(Clinical interpretation of variants in patients with disease)有着重...
The one PTV identified in INTERVAL (p.Trp3926*) is located at the final amino acid of the bassoon protein and is therefore unlikely to affect expression levels (note that the LOFTEE in silico stop-gain filter for low-confidence loss of function based on the ‘50-bp rule’ does not apply...
Protein-truncating variants can have profound effects on gene function and are critical for clinical genome interpretation and generating therapeutic hypotheses, but their relevance to medical phenotypes has not been systematically assessed. Here, we characterize the effect of 18,228 protein-truncating ...
a, Case–control enrichment of rare (minor allele count ≤ 5) protein-truncating, missense and synonymous variants in all ancestries combined. The PGC3SEQ results were derived from 11,580 individuals with SCZ and 10,555 controls and are shown in red/orange. We conducted the same analysi...
A meta-analysis was then performed on protein-truncating variants (PTVs) identified in the studies for an association with breast cancer risk. A total of 10,209 publications were identified, of which 64 studies comprising a total of 25,418 cases and 52,322 controls in the 6 interrogated ...
Using this distribution of selection coefficients for heterozygous protein-truncating variants (PTVs), we provide corresponding Bayesian estimates for individual genes. We find that genes under the strongest selection are enriched in embryonic lethal mouse knockouts, Mendelian disease-associated genes, and ...
we assessed the relevance of protein-truncating variant (PTV) gene burden on individual and parental survival. We identified four exome-wide significant (P < 4.2 × 10−7) human lifespan genes,BRCA1,BRCA2,ATMandTET2. Gene and gene-set, PTV-burden, phenome-wide association studies...
RESULTS KHDC3L mutations in three unrelated patients and a novel protein-truncating mutation KHDC3L mutation analysis in a cohort of 29 unrelated patients, 26 singleton and 3 familial cases, each with at least 2 HMs revealed 2 mutations in 3 patients (Table 1). The first mutation was a ...
confidence intervals throughout (a)– (c). ID/DD, intellectual disability / developmental delay; ASD, autism spectrum disorder; PTV, protein truncating variant; pLI, probability of loss-of-function intolerance; NS, not significant. Supplementary Figure 4 Recalibrating VQSLOD for transmission of ...
· Chikashi Ishioka Evaluation of the diagnostic accuracy of the stop codon (SC) assay for identifying protein-truncating mutations in the BRCA1 and BRCA2 genes in familial breast cancer Received: October 9, 2002 / Accepted: December 3, 2002 Abstract Screening for protein-truncating mutations of ...