ライフサイエンスコーパス: VUS

1 VUS were introduced into the endogenous Msh2 gene of mou

2 VUSs with evidence in favor of causality were those that

3 A total of 133 VUSs had odds of at least 100 : 1 in favor of neutrality

4 r volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutatio

5 Nineteen of the 59 VUS were identified as pathogenic.

6 revealed all to be deleterious, including a VUS.

7 the assessment: co-occurrence in trans of a VUS with known deleterious mutations; detailed analysis,

8 ed disease causality for BRCA1 p.V1688del, a VUS recurrent in Italian breast/ovarian cancer families.

9 nine allowed the detection of MMR-abrogating VUS.

10 When applied to 33 additional VUS, the classifier identified eight with 99% or more pr

11 ovide a probability of pathogenicity for all VUS in the BRCA2 DBD, suggesting that the assay can be u

12 Over half of these variants are annotated as VUS by clinical diagnostic laboratories.

13 functional assay to characterize eight BRCA2 VUS that affect highly conserved amino acid residues and

14 n to determine the cancer relevance of BRCA2 VUS.

15 nt an adjunct to sequencing for categorizing VUS or may represent a stand-alone measure for assessing

16 ed to provide an overall assessment for each VUS.

17 igh probability that the corresponding human VUS is pathogenic.

18 e assignment of pathogenicity to these human VUS and validates the approach described here as a diagn

19 The majority of identified VUS occur only in one to two individuals; these variants

20 of personal and family history of cancer in VUS-carrying probands; and, in a subset of probands, an

21 y uninformative germline findings, including VUS.

22 l analyses of one variant, a synonymous LMNA VUS, demonstrated segregation with cardiomyopathy affect

23 A total of 479 individuals had 1 or more VUS (38%; 95% CI, 35%-41%).

24 ies from benign variants and categorize most VUS as benign.

25 orphisms and was used to investigate 59 Msh2 VUS.

26 HWA is able to classify MLH1, MSH2, and MSH6 VUSs as either benign or pathogenic with high accuracy.

27 LP] or pathogenic [P]) versus nonactionable (VUS, likely benign, or benign) calls were 95% concordant

28 lapping clinical features, each with a novel VUS in the middle domain of DNM1L (p.G350R and p.E379K).

29 with the p.E379K variant also has a de novo VUS in pyruvate dehydrogenase 1 (PDHA1) affecting the sa

30 tegies for screening and characterization of VUS.

31 Classification of VUS as neutral will have immediate benefit for those ind

32 an important role, careful consideration of VUS reveals it to be a nebulous description of genomic i

33 method that can predict the pathogenicity of VUS that does not require familial information or segreg

34 ilial data to determine the pathogenicity of VUS.

35 thod for inferring the clinical relevance of VUS in the DBD of BRCA2 using 18 established nonpathogen

36 a similar HWA to allow for classification of VUSs in genes associated with Lynch syndrome using data

37 mented a HWA to aid in the classification of VUSs in genes associated with Lynch syndrome.

38 hermore, 95% of individuals had at least one VUS.

39 Sample size determination based on AUC or VUS would not only guarantee an overall correct classifi

40 ference between the two approximate AUCs (or VUSs) is below a pre-specified threshold.

41 then used to evaluate the associated AUCs or VUSs, whose accuracies are validated using Monte Carlo s

42 facilitate the identification of pathogenic VUS, we have developed an in cellulo genetic screen-base

43 s, we used computational tools to prioritize VUS and developed a cell-based minigene splicing assay t

44 s variants of unknown clinical significance (VUS) due to the availability of very limited information

45 variants of uncertain clinical significance (VUS).

46 umber of variants of uncertain significance (VUS) are being identified, the unclassified biological e

47 ions and variants of uncertain significance (VUS) in 180 medically relevant genes, including all ACMG

48 ny BRCA2 variants of uncertain significance (VUS) to breast cancer has not been determined due to lim

49 fied as a variant of uncertain significance (VUS), 191 (32%) as pathogenic, and 34 (6%) as benign.

50 of these variants of uncertain significance (VUS), focusing on mutator S homolog 2 (MSH2).

51 2 carry a variant of uncertain significance (VUS), making clinical management less certain.

52 rols and variants of uncertain significance (VUS).

53 genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%).

54 syndrome, variants of unclear significance (VUS), rather than an obviously pathogenic mutations, are

55 ay uncover variants of unknown significance (VUS) that require functional validation.

56 ssified as variants of unknown significance (VUS).

57 f variants of unknown clinical significance (VUSs).

58 and 348 variants of uncertain significance (VUSs) classified as high confidence from ClinVar.

59 ation of variants of uncertain significance (VUSs) in BRCA1 and BRCA2.

60 3 sequence variants of unknown significance (VUSs) in the BRCA genes.

61 nation, "variant of uncertain significance" (VUS).

62 The uncertainty of whether such VUS inactivate MMR, and therefore are pathogenic, preclu

63 and the Volume Under the ROC hyper-Surface (VUS) for three or more classes.

64 the pathogenic variants and 75 (22%) of the VUSs.

65 o was computed under the hypothesis that the VUSs were equivalent to an "average" deleterious mutatio

66 ranging from pathogenic/likely pathogenic to VUS, a discrepancy that may alter medical management.

67 Of the 33 previously unclassified VUS studied, we found evidence of neutrality for 21.

68 y half of these critical residues match with VUS previously identified in individuals suspected of Ly

69 Half of average-risk patients with VUS undergo BLM, suggesting a limited understanding of r