Activity

Filter

Cancel
Date Panel Item Activity
25 actions
Pancreatitis v2.10 TRPV6 Miranda Durkie changed review comment from: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature

Additional paper: PMID: 34923708 . Sequenced cohort of HCP and ICP and patients and identified 25 novel TRPV6 missense variants. Used functional Ca2+ assay to show 8 are functionally defective. Revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Therefore likely susceptibility allele as part of polygenic model. Keep at amber rating; to: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature

Additional paper: PMID: 34923708 added 20/01/2022. Sequenced cohort of HCP and ICP and patients and identified 25 novel TRPV6 missense variants. Used functional Ca2+ assay to show 8 are functionally defective. Revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Therefore likely susceptibility allele as part of polygenic model. Keep at amber rating 22/01/22
Pancreatitis v2.10 TRPV6 Miranda Durkie changed review comment from: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature; to: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature

Additional paper: PMID: 34923708 . Sequenced cohort of HCP and ICP and patients and identified 25 novel TRPV6 missense variants. Used functional Ca2+ assay to show 8 are functionally defective. Revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Therefore likely susceptibility allele as part of polygenic model. Keep at amber rating
Pancreatitis v1.4 CFTR Ivone Leong Marked gene: CFTR as ready
Pancreatitis v1.4 CFTR Ivone Leong Added comment: Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Pancreatitis v1.4 CFTR Ivone Leong Gene: cftr has been classified as Green List (High Evidence).
Pancreatitis v1.4 CFTR Ivone Leong reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.3 CFTR Ivone Leong Source NHS GMS was added to CFTR.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pancreatitis v0.46 CFTR Ellen McDonagh Phenotypes for gene: CFTR were changed from {Pancreatitis, hereditary} 167800 to {Pancreatitis, hereditary} 167800; Cystic fibrosis 219700
Pancreatitis v0.45 CFTR Ellen McDonagh Classified gene: CFTR as Green List (high evidence)
Pancreatitis v0.45 CFTR Ellen McDonagh Added comment: Comment on list classification: This gene has been promoted from Amber to Green, for the biallelic mode of inheritance, due to comments from Dr Ellen Thomas that exocrine pancreas dysfunction is an indication for diagnostic Cystic Fibrosis testing, and therefore this panel should cover the CFTR gene.
Pancreatitis v0.45 CFTR Ellen McDonagh Gene: cftr has been classified as Green List (High Evidence).
Pancreatitis v0.44 CFTR Ellen McDonagh Added comment: Comment on mode of inheritance: Changed to the biallelic form.
Pancreatitis v0.44 CFTR Ellen McDonagh Mode of inheritance for gene: CFTR was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Pancreatitis v0.43 CFTR Ellen Thomas reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cystic fibrosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Pancreatitis v0.20 CFTR Eleanor Williams Classified gene: CFTR as Amber List (moderate evidence)
Pancreatitis v0.20 CFTR Eleanor Williams Added comment: Comment on list classification: Rating Amber based on feedback from Genomics England clinical team.
Pancreatitis v0.20 CFTR Eleanor Williams Gene: cftr has been classified as Amber List (Moderate Evidence).
Pancreatitis v0.18 CFTR Eleanor Williams Phenotypes for gene: CFTR were changed from to {Pancreatitis, hereditary} 167800
Pancreatitis v0.17 CFTR Eleanor Williams Publications for gene: CFTR were set to
Pancreatitis v0.16 CFTR Eleanor Williams Mode of inheritance for gene: CFTR was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pancreatitis v0.15 CFTR Eleanor Williams edited their review of gene: CFTR: Changed publications: 9725921, 15987793, 16134171, 16193325, 11729110, 23951356, 22427236, 25033378, 22658665, 26856995, 27555793, 1345141, 15749233, 25033378, 20977904, 22427236; Changed phenotypes: {Pancreatitis, hereditary} 167800; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pancreatitis v0.15 CFTR Eleanor Williams commented on gene: CFTR: Checking with Genomics England Clinical team as to the correct rating for this gene.
Pancreatitis v0.15 CFTR Eleanor Williams commented on gene: CFTR
Pancreatitis CFTR Ioannis Sarantitis reviewed gene: CFTR
Pancreatitis CFTR Ellen McDonagh Added gene to panel