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| Monogenic diabetes v3.8 | WFS1 |
Ida Ertmanska changed review comment from: PMID: 40779032 Sriram et al., 2025 Cohort of 2,571 unrelated individuals of European ancestry with clinically suspected MODY. Genes assessed: APPL1 NM_012096.3, HNF1A NM_000545.8, NEUROD1 NM_002500.5, PDX1 NM_000209.4, RFX6 NM_173560.4, and WFS1 NM_006005.3. "Frequency and co-segregation analysis examined specific, previously published variants and did not assess if other rare variants in these genes cause MODY." - MODY cohort showed no enrichment for protein-truncating variants or damaging missense variants in WFS1 (p > 0.05). Other genes (NEUROD1 and PDX1) showed enrichment in the MODY cohort. - Study identified a WFS1 p.Trp314Arg carrier: diagnosed with diabetes at age 33, BMI 22.9, no family history of diabetes, no known other pathogenic variant. PMID: 39221226 Wu et al., 2024 Whole exome seq in 165 early-onset diabetes patients. Detected WFS1 compound heterozygous variants in two patients with Wolfram Syndrome-Like disorders. WFS1 heterozygous variants were identified in patients P3-P5: c.1289C>T, p.S430L; c.1552A>G, p.M518V; c.676C>T, p.Q226*. All variants in this study affect exons 6 or 8 of WFS1. Heterozygous patients all had family history of diabetes, and were all diagnosed at 25 years old. Diagnosed with MODY rather than Wolfram Syndrome. P1: female, diagnosed with diabetes at age 25years, compound het for WFS1 c.639_640dupGG, p.A214fs*74/c.985T>A, p.F329I; mother and father heterozygous for a variant each (both diagnosed with diabetes over age 35 years). Some affected family members were carriers of either variant, some had neither. Proband did not present with ketoacidosis, optic atrophy, deafness, or diabetes insipidus. P2: female, diagnosed with diabetes at 13yo, compound het for WFS1 c.1280T>G, p.I427S/c.911T>C, p.I304T; no neurological, psychiatric, or high-frequency hearing issues, or optic nerve atrophy; brother, mother and father were heterozygous for a WFS1 variant each, not affected. Functional analysis verified the impaired function of the WFS1 compound heterozygous variants: p.A214fs*74 and p.I427S significantly reduced wolframin levels (absent/near absent); p.I427S and the compound heterozygous p.I427S/p.I304T variants significantly activated the ERSE reporter, indicating high ER stress PMID: 29207974 Bansal et al., 2017 Sequenced 22 diabetes related genes in almost 7000 individuals. Identified an individual with early onset diabetes (onset at 14 years old; no additional phenotypes associated with Wolfram syndrome), homozygous for WFS1: c.1672C > T; p.R558C. PMID: 28271591 Morikawa et al. 2017 Japanese female patient with a de novo heterozygous WFS1 c.973_984del12, p.Asn325_Ile328del variant (not in gnomAD v4.1.0. She presented with impaired growth, bilateral congenital cataracts, severe hypermetropia, severe bilateral hearing loss, delayed development, insulin dependent diabetes mellitus - diagnosed with Wolfram Syndrome. In vitro testing showed that the WFS1 variant has a dominant negative effect, increasing ER stress. PMID: 23903355 Bonnycastle et al., 2013 Large Finnish pedigree with AD diabetes, WFS1 p.Trp314Arg variant co-segregated completely with disease. Seq method: exome/Sanger. Age of diabetes onset ranged from 18 to 51 years. No history of ketoacidosis, 7/8 affected individuals treated with insulin. Functionally p.Trp314Arg appears to reduce the ability of WFS1 to protect against ER stress (study in HEK293T cells). WFS1 is associated with AR Wolfram syndrome 1, OMIM:222300 (OMIM accessed 27th Feb 2026). The gene-disease associations between WFS1 and AR Wolfram syndrome & WFS1 and AD Wolfram-like syndrome are both classified as Definitive in ClinGen - diabetes being a feature of both.; to: PMID: 40779032 Sriram et al., 2025 Cohort of 2,571 unrelated individuals of European ancestry with clinically suspected MODY. Genes assessed: APPL1 NM_012096.3, HNF1A NM_000545.8, NEUROD1 NM_002500.5, PDX1 NM_000209.4, RFX6 NM_173560.4, and WFS1 NM_006005.3. "Frequency and co-segregation analysis examined specific, previously published variants and did not assess if other rare variants in these genes cause MODY." - MODY cohort showed no enrichment for protein-truncating variants or damaging missense variants in WFS1 (p > 0.05). Other genes (NEUROD1 and PDX1) showed enrichment in the MODY cohort. - Study identified a WFS1 p.Trp314Arg carrier: diagnosed with diabetes at age 33, BMI 22.9, no family history of diabetes, no known other pathogenic variant. PMID: 39221226 Wu et al., 2024 Whole exome seq in 165 early-onset diabetes patients. Detected WFS1 compound heterozygous variants in two patients with Wolfram Syndrome-Like disorders. WFS1 heterozygous variants were identified in patients P3-P5: c.1289C>T, p.S430L; c.1552A>G, p.M518V; c.676C>T, p.Q226*. All variants in this study affect exons 6 or 8 of WFS1. Heterozygous patients all had family history of diabetes, and were all diagnosed at 25 years old. Diagnosed with MODY rather than Wolfram Syndrome. P1: female, diagnosed with diabetes at age 25years, compound het for WFS1 c.639_640dupGG, p.A214fs*74/c.985T>A, p.F329I; mother and father heterozygous for a variant each (both diagnosed with diabetes over age 35 years). Some affected family members were carriers of either variant, some had neither. Proband did not present with ketoacidosis, optic atrophy, deafness, or diabetes insipidus. P2: female, diagnosed with diabetes at 13yo, compound het for WFS1 c.1280T>G, p.I427S/c.911T>C, p.I304T; no neurological, psychiatric, or high-frequency hearing issues, or optic nerve atrophy; brother, mother and father were heterozygous for a WFS1 variant each, not affected. Functional analysis verified the impaired function of the WFS1 compound heterozygous variants: p.A214fs*74 and p.I427S significantly reduced wolframin levels (absent/near absent); p.I427S and the compound heterozygous p.I427S/p.I304T variants significantly activated the ERSE reporter, indicating high ER stress PMID: 29207974 Bansal et al., 2017 Sequenced 22 diabetes related genes in almost 7000 individuals. Identified an individual with early onset diabetes (onset at 14 years old; no additional phenotypes associated with Wolfram syndrome), homozygous for WFS1: c.1672C > T; p.R558C. PMID: 28271591 Morikawa et al. 2017 Japanese female patient with a de novo heterozygous WFS1 c.973_984del12, p.Asn325_Ile328del variant (not in gnomAD v4.1.0. She presented with impaired growth, bilateral congenital cataracts, severe hypermetropia, severe bilateral hearing loss, delayed development, insulin dependent diabetes mellitus - diagnosed with Wolfram Syndrome. In vitro testing showed that the WFS1 variant has a dominant negative effect, increasing ER stress. PMID: 23903355 Bonnycastle et al., 2013 Large Finnish pedigree with AD diabetes, WFS1 p.Trp314Arg variant co-segregated completely with disease. Seq method: exome/Sanger. Age of diabetes onset ranged from 18 to 51 years. No history of ketoacidosis, 7/8 affected individuals treated with insulin. Functionally p.Trp314Arg appears to reduce the ability of WFS1 to protect against ER stress (study in HEK293T cells). WFS1 is associated with AR Wolfram syndrome 1, OMIM:222300 (OMIM accessed 27th Feb 2026). The gene-disease associations between WFS1 and AR Wolfram syndrome, AD Wolfram-like syndrome, and AD Nonsyndromic hearing loss are all classified as Definitive in ClinGen. |
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| Monogenic diabetes v3.8 | APPL1 |
Ida Ertmanska changed review comment from: PMID: 40779032 Sriram et al., 2025 Cohort of 2,571 unrelated individuals of European ancestry with clinically suspected MODY. Genes assessed: APPL1 NM_012096.3, HNF1A NM_000545.8, NEUROD1 NM_002500.5, PDX1 NM_000209.4, RFX6 NM_173560.4, and WFS1 NM_006005.3. Frequency and co-segregation analysis examined specific, previously published variants and did not assess if other rare variants in these genes cause MODY. Conflicting evidence: - 8/23 individuals originally reported in PMID: 26073777 did not have diabetes, despite carrying the variant and being over age 25 (potentially reduced penetrance/have not yet developed the disease) - Authors claim LOF variants seem generally common in gnomAD - too common to cause MODY (however, pLI score for APPL1 is 0.88 - likely to be a dosage sensitive gene) - MODY cohort showed no enrichment for protein-truncating variants or damaging missense variants in APPL1. Other genes (NEUROD1 and PDX1) showed enrichment in the MODY cohort. PMID: 38464380 Shi et al., 2024 A total of five novel APPL1 mutations were identified in patients with diabetes (onset at ages 8, 12, 13, 21, and 39 years), including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Seq method: WES. Of these 5, 2 variants were classed as pathogenic after analysis: APPL1 c.1894G>T (p.Asp632Tyr) and c.1595G>A (p.Arg532Gln). These variants have 2 and 13 heterozygotes reported in gnomAD v4.1.0, respectively. Incomplete pentrance noted - P3 and his grandfather had diabetes, but his father did not (also het for APPL1 p.Arg532Gln). Patient 1 had an affected father and grandmother, but genotyping was not done. Patients 2, 4, and 5 were concluded to carry non-pathogenic APPL1 variants, and were diagnosed with type 2 diabetes instead. Functional assessment: HEK293 cells transfected with mutated plasmids; the mRNA expression level of APPL1 Asp632Tyr variant decreased by 98% (P = 0.001) compared with WT-APPL1, resulting in no protein expression; mRNA expression of Arg532Gln variant decreased by 14%; protein expression of the p.Arg532Gln variant was significantly reduced compared with WT APPL1. PMID: 32854233 Ivanoshchuk et al., 2020 Cohort of 151 Russian patients with early-onset MODY/Type 2 diabetes diagnosis, sequenced using WES or targeted sequencing. APPL1 polymorphism rs11544593 was flagged as a risk factor, but no pathogenic APPL1 variants detected. PMID: 26073777 Prudente et al., 2015 Report of 2 large families with high prevalence of diabetes. Variants identified: c.1655T>A, p.Leu552* (not in gnomAD v4.1.0) and c.280G>A, p.Asp94Asn (5 heterozygous individuals reported in gnomAD v4.1.0). Seq method: WES. F1: Italian family, APPL1 c.1655T>A, p.Leu552* detected; individuals diagnosed with diabetes aged 20-50. F2: US family, APPl1 c.280G>A, p.Asp94Asn detected; individuals diagnosed with diabetes aged 10-48. Lack of mutations in the six most common MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B, and NEUROD1) was a prerequisite for this study and confirmed in the two families. Functional evidence: the p.Leu552∗ alteration abolishes APPL1 protein expression in HepG2 transfected cells; p.Asp94Asn alteration causes significant reduction in the enhancement of the insulin-stimulated AKT2 and GSK3β phosphorylation that is observed after wild-type APPL1 transfection. APPL1 has a key regulatory role in glucose metabolism. The gene was reclassified from Moderate to Refuted by ClinGen in Feb 2026 (Monogenic diabetes panel), on the basis of evidence presented in PMID: 40779032.; to: EVIDENCE AGAINST ASSOCIATION: PMID: 40779032 Sriram et al., 2025 Cohort of 2,571 unrelated individuals of European ancestry with clinically suspected MODY. Genes assessed: APPL1 NM_012096.3, HNF1A NM_000545.8, NEUROD1 NM_002500.5, PDX1 NM_000209.4, RFX6 NM_173560.4, and WFS1 NM_006005.3. Frequency and co-segregation analysis examined specific, previously published variants and did not assess if other rare variants in these genes cause MODY. Conflicting evidence: - 8/23 individuals originally reported in PMID: 26073777 did not have diabetes, despite carrying the variant and being over age 25 (potentially reduced penetrance/have not yet developed the disease) - Authors claim LOF variants seem generally common in gnomAD - too common to cause MODY (however, pLI score for APPL1 is 0.88 - likely to be a dosage sensitive gene) - MODY cohort showed no enrichment for protein-truncating variants or damaging missense variants in APPL1. Other genes (NEUROD1 and PDX1) showed enrichment in the MODY cohort. PMID: 32854233 Ivanoshchuk et al., 2020 Cohort of 151 Russian patients with early-onset MODY/Type 2 diabetes diagnosis, sequenced using WES or targeted sequencing. APPL1 polymorphism rs11544593 was flagged as a risk factor, but no pathogenic APPL1 variants detected. The gene was reclassified from Moderate to Refuted by ClinGen in Feb 2026 (Monogenic diabetes panel), on the basis of evidence presented in PMID: 40779032. EVIDENCE SUPPORTING ASSOCIATION: PMID: 38464380 Shi et al., 2024 A total of five novel APPL1 mutations were identified in patients with diabetes (onset at ages 8, 12, 13, 21, and 39 years), including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Seq method: WES. Of these 5, 2 variants were classed as pathogenic after analysis: APPL1 c.1894G>T (p.Asp632Tyr) and c.1595G>A (p.Arg532Gln). These variants have 2 and 13 heterozygotes reported in gnomAD v4.1.0, respectively. Incomplete pentrance noted - P3 and his grandfather had diabetes, but his father did not (also het for APPL1 p.Arg532Gln). Patient 1 had an affected father and grandmother, but genotyping was not done. Patients 2, 4, and 5 were concluded to carry non-pathogenic APPL1 variants, and were diagnosed with type 2 diabetes instead. Functional assessment: HEK293 cells transfected with mutated plasmids; the mRNA expression level of APPL1 Asp632Tyr variant decreased by 98% (P = 0.001) compared with WT-APPL1, resulting in no protein expression; mRNA expression of Arg532Gln variant decreased by 14%; protein expression of the p.Arg532Gln variant was significantly reduced compared with WT APPL1. PMID: 26073777 Prudente et al., 2015 Report of 2 large families with high prevalence of diabetes. Variants identified: c.1655T>A, p.Leu552* (not in gnomAD v4.1.0) and c.280G>A, p.Asp94Asn (5 heterozygous individuals reported in gnomAD v4.1.0). Seq method: WES. F1: Italian family, APPL1 c.1655T>A, p.Leu552* detected; individuals diagnosed with diabetes aged 20-50. F2: US family, APPl1 c.280G>A, p.Asp94Asn detected; individuals diagnosed with diabetes aged 10-48. Lack of mutations in the six most common MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B, and NEUROD1) was a prerequisite for this study and confirmed in the two families. Functional evidence: the p.Leu552∗ alteration abolishes APPL1 protein expression in HepG2 transfected cells; p.Asp94Asn alteration causes significant reduction in the enhancement of the insulin-stimulated AKT2 and GSK3β phosphorylation that is observed after wild-type APPL1 transfection. APPL1 has a key regulatory role in glucose metabolism. |
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| Monogenic diabetes v3.8 | APPL1 |
Ida Ertmanska changed review comment from: PMID: 40779032 Sriram et al., 2025 Cohort of 2,571 unrelated individuals of European ancestry with clinically suspected MODY. Genes assessed: APPL1 NM_012096.3, HNF1A NM_000545.8, NEUROD1 NM_002500.5, PDX1 NM_000209.4, RFX6 NM_173560.4, and WFS1 NM_006005.3. Frequency and co-segregation analysis examined specific, previously published variants and did not assess if other rare variants in these genes cause MODY. Conflicting evidence: - 8/23 individuals originally reported in PMID: 26073777 did not have diabetes, despite carrying the variant and being over age 25 (potentially reduced penetrance/have not yet developed the disease) - Authors claim LOF variants seem generally common in gnomAD - too common to cause MODY (however, pLI score for APPL1 is 0.88 - likely to be a dosage sensitive gene) - MODY cohort showed no enrichment for protein-truncating variants or damaging missense variants in APPL1. Other genes (NEUROD1 and PDX1) showed enrichment in the MODY cohort. PMID: 38464380 Shi et al., 2024 A total of five novel APPL1 mutations were identified in patients with diabetes (onset at ages 8, 12, 13, 21, and 39 years), including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Seq method: WES. Of these 5, 2 variants were classed as pathogenic after analysis: APPL1 c.1894G>T (p.Asp632Tyr) and c.1595G>A (p.Arg532Gln). These variants have 2 and 13 heterozygotes reported in gnomAD v4.1.0, respectively. Incomplete pentrance noted - P3 and his grandfather had diabetes, but his father did not (also het for APPL1 p.Arg532Gln). Patient 1 had an affected father and grandmother, but genotyping was not done. Patients 2, 4, and 5 were concluded to carry non-pathogenic APPL1 variants, and were diagnosed with type 2 diabetes instead. Functional assessment: HEK293 cells transfected with mutated plasmids; the mRNA expression level of APPL1 Asp632Tyr variant decreased by 98% (P = 0.001) compared with WT-APPL1, resulting in no protein expression; mRNA expression of Arg532Gln variant decreased by 14%; protein expression of the p.Arg532Gln variant was significantly reduced compared with WT APPL1. PMID: 32854233 Ivanoshchuk et al., 2020 Cohort of 151 Russian patients with early-onset MODY/Type 2 diabetes diagnosis, sequenced using WES or targeted sequencing. APPL1 polymorphism rs11544593 was flagged as a risk factor, but no pathogenic APPL1 variants detected. PMID: 26073777 Prudente et al., 2015 Report of 2 large families with high prevalence of diabetes. Variants identified: c.1655T>A, p.Leu552* (not in gnomAD v4.1.0) and c.280G>A, p.Asp94Asn (5 heterozygous individuals reported in gnomAD v4.1.0). Seq method: WES. F1: Italian family, APPL1 c.1655T>A, p.Leu552* detected; individuals diagnosed with diabetes aged 20-50. F2: US family, APPl1 c.280G>A, p.Asp94Asn detected; individuals diagnosed with diabetes aged 10-48. Lack of mutations in the six most common MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B, and NEUROD1) was a prerequisite for this study and confirmed in the two families. Functional evidence: the p.Leu552∗ alteration abolishes APPL1 protein expression in HepG2 transfected cells; p.Asp94Asn alteration causes significant reduction in the enhancement of the insulin-stimulated AKT2 and GSK3β phosphorylation that is observed after wild-type APPL1 transfection. APPL1 has a key regulatory role in glucose metabolism. The gene was reclassified from Moderate to Refuted by ClinGen in Feb 2026 (Monogenic diabetes panel), on the basis of evidence presented in PMID: 40779032.; to: PMID: 40779032 Sriram et al., 2025 Cohort of 2,571 unrelated individuals of European ancestry with clinically suspected MODY. Genes assessed: APPL1 NM_012096.3, HNF1A NM_000545.8, NEUROD1 NM_002500.5, PDX1 NM_000209.4, RFX6 NM_173560.4, and WFS1 NM_006005.3. Frequency and co-segregation analysis examined specific, previously published variants and did not assess if other rare variants in these genes cause MODY. Conflicting evidence: - 8/23 individuals originally reported in PMID: 26073777 did not have diabetes, despite carrying the variant and being over age 25 (potentially reduced penetrance/have not yet developed the disease) - Authors claim LOF variants seem generally common in gnomAD - too common to cause MODY (however, pLI score for APPL1 is 0.88 - likely to be a dosage sensitive gene) - MODY cohort showed no enrichment for protein-truncating variants or damaging missense variants in APPL1. Other genes (NEUROD1 and PDX1) showed enrichment in the MODY cohort. PMID: 38464380 Shi et al., 2024 A total of five novel APPL1 mutations were identified in patients with diabetes (onset at ages 8, 12, 13, 21, and 39 years), including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Seq method: WES. Of these 5, 2 variants were classed as pathogenic after analysis: APPL1 c.1894G>T (p.Asp632Tyr) and c.1595G>A (p.Arg532Gln). These variants have 2 and 13 heterozygotes reported in gnomAD v4.1.0, respectively. Incomplete pentrance noted - P3 and his grandfather had diabetes, but his father did not (also het for APPL1 p.Arg532Gln). Patient 1 had an affected father and grandmother, but genotyping was not done. Patients 2, 4, and 5 were concluded to carry non-pathogenic APPL1 variants, and were diagnosed with type 2 diabetes instead. Functional assessment: HEK293 cells transfected with mutated plasmids; the mRNA expression level of APPL1 Asp632Tyr variant decreased by 98% (P = 0.001) compared with WT-APPL1, resulting in no protein expression; mRNA expression of Arg532Gln variant decreased by 14%; protein expression of the p.Arg532Gln variant was significantly reduced compared with WT APPL1. PMID: 32854233 Ivanoshchuk et al., 2020 Cohort of 151 Russian patients with early-onset MODY/Type 2 diabetes diagnosis, sequenced using WES or targeted sequencing. APPL1 polymorphism rs11544593 was flagged as a risk factor, but no pathogenic APPL1 variants detected. PMID: 26073777 Prudente et al., 2015 Report of 2 large families with high prevalence of diabetes. Variants identified: c.1655T>A, p.Leu552* (not in gnomAD v4.1.0) and c.280G>A, p.Asp94Asn (5 heterozygous individuals reported in gnomAD v4.1.0). Seq method: WES. F1: Italian family, APPL1 c.1655T>A, p.Leu552* detected; individuals diagnosed with diabetes aged 20-50. F2: US family, APPl1 c.280G>A, p.Asp94Asn detected; individuals diagnosed with diabetes aged 10-48. Lack of mutations in the six most common MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B, and NEUROD1) was a prerequisite for this study and confirmed in the two families. Functional evidence: the p.Leu552∗ alteration abolishes APPL1 protein expression in HepG2 transfected cells; p.Asp94Asn alteration causes significant reduction in the enhancement of the insulin-stimulated AKT2 and GSK3β phosphorylation that is observed after wild-type APPL1 transfection. APPL1 has a key regulatory role in glucose metabolism. The gene was reclassified from Moderate to Refuted by ClinGen in Feb 2026 (Monogenic diabetes panel), on the basis of evidence presented in PMID: 40779032. |
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| Monogenic diabetes v2.37 | TRMT10A |
Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes: failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies;young onset diabetes, short stature and microcephaly with intellectual disability;Autosomal recessive juvenile-onset diabetes with microcephaly, epilepsy and intellectual disability;Microcephaly, short stature, and impaired glucose metabolism 1, 616033 |
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| Monogenic diabetes v2.37 | TRMT10A | Ivone Leong Phenotypes for gene: TRMT10A were changed from failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies; young onset diabetes, short stature and microcephaly with intellectual disability; Autosomal recessive juvenile-onset diabetes with microcephaly, epilepsy and intellectual disability; Microcephaly, short stature, and impaired glucose metabolism 1, 616033 to Microcephaly, short stature, and impaired glucose metabolism 1, OMIM:616033 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v2.17 | HNF1B |
Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes: Transient neonatal diabetes;Renal Cysts and Diabetes Syndrome;Diabetes mellitus, noninsulin-dependent, 125853;Maturity-Onset Diabetes Of The Young;RCAD;renal malformation;{Renal cell carcinoma}, 144700;Renal cysts and diabetes syndrome, 137920;RENAL CYSTS AND DIABETES SYNDROME |
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| Monogenic diabetes v2.17 | HNF1B | Ivone Leong Phenotypes for gene: HNF1B were changed from Transient neonatal diabetes; Renal Cysts and Diabetes Syndrome; Diabetes mellitus, noninsulin-dependent, 125853; Maturity-Onset Diabetes Of The Young; RCAD; renal malformation; {Renal cell carcinoma}, 144700; Renal cysts and diabetes syndrome, 137920; RENAL CYSTS AND DIABETES SYNDROME to transient neonatal diabetes mellitus (disease), MONDO:0020525; Type 2 diabetes mellitus, OMIM:125853; maturity-onset diabetes of the young (disease), MONDO:0018911 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v2.15 | HNF1A |
Ivone Leong Added comment: Comment on phenotypes: Phenotypes were previous: Hepatic adenoma, somatic, 142330;Maturity-Onset Diabetes Of The Young;{Diabetes mellitus, insulin-dependent}, 222100;Renal cell carcinoma, 144700;MODY, type III, 600496{Diabetes mellitus, noninsulin-dependent, 2}, 125853{Diabetes mellitus, insulin-dependent}, 222100Hepatic adenoma, somatic, 142330Renal cell carcinoma, 144700Diabetes mellitus, insulin-dependent, 20, 612520;Diabetes mellitus, insulin-dependent, 20, 612520;MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3;MODY3;Maturity-onset diabetes of the young (MODY);{Diabetes mellitus, noninsulin-dependent, 2}, 125853;MODY, type III, 600496;Maturity Onset Diabetes of the Young |
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| Monogenic diabetes v2.15 | HNF1A | Ivone Leong Phenotypes for gene: HNF1A were changed from Hepatic adenoma, somatic, 142330; Maturity-Onset Diabetes Of The Young; {Diabetes mellitus, insulin-dependent}, 222100; Renal cell carcinoma, 144700; MODY, type III, 600496{Diabetes mellitus, noninsulin-dependent, 2}, 125853{Diabetes mellitus, insulin-dependent}, 222100Hepatic adenoma, somatic, 142330Renal cell carcinoma, 144700Diabetes mellitus, insulin-dependent, 20, 612520; Diabetes mellitus, insulin-dependent, 20, 612520; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3; MODY3; Maturity-onset diabetes of the young (MODY); {Diabetes mellitus, noninsulin-dependent, 2}, 125853; MODY, type III, 600496; Maturity Onset Diabetes of the Young to Diabetes mellitus, insulin-dependent, 20, OMIM:612520; {Diabetes mellitus, noninsulin-dependent, 2}, OMIM:125853; MODY, type III, OMIM:600496 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v2.7 | CEL | Ivone Leong Phenotypes for gene: CEL were changed from Maturity-onset diabetes of the young, type VIII, 609812; Diabetes and pancreatic exocrine dysfunction to Maturity-onset diabetes of the young, type VIII, OMIM:609812; Diabetes and pancreatic exocrine dysfunction | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v1.37 | TRMT10A | Ivone Leong Phenotypes for gene: TRMT10A were changed from failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies; young onset diabetes, short stature and microcephaly with intellectual disability to failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies; young onset diabetes, short stature and microcephaly with intellectual disability; Autosomal recessive juvenile-onset diabetes with microcephaly, epilepsy and intellectual disability; Microcephaly, short stature, and impaired glucose metabolism 1, 616033 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v1.18 | CEL | Ivone Leong Phenotypes for gene: CEL were changed from Maturity-onset diabetes of the young, type VIII, 609812 to Maturity-onset diabetes of the young, type VIII, 609812; Diabetes and pancreatic exocrine dysfunction | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v1.6 | CEL | Ivone Leong Publications for gene: CEL were set to 16369531 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v1.1 | CEL | Jayne Houghton reviewed gene: CEL: Rating: GREEN; Mode of pathogenicity: ; Publications: 24062244, 21784842, 19760265, 18544793, 17989309, 16369531, 27650499, 25160620; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.16 | CEL | Ivone Leong Classified gene: CEL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.16 | CEL | Ivone Leong Added comment: Comment on list classification: Promoted from red to green as advised via email communication with Jane Houghton (South West GLH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.16 | CEL | Ivone Leong Gene: cel has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.8 | CEL | Ivone Leong reviewed gene: CEL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.7 | CEL | Ivone Leong Source NHS GMS was added to CEL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.2 | HNF1B | Ellen McDonagh Added phenotypes Transient neonatal diabetes; Renal Cysts and Diabetes Syndrome; Diabetes mellitus, noninsulin-dependent, 125853; Maturity-Onset Diabetes Of The Young; RCAD; renal malformation; {Renal cell carcinoma}, 144700; Renal cysts and diabetes syndrome, 137920; RENAL CYSTS AND DIABETES SYNDROME for gene: HNF1B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.2 | HNF1A | Ellen McDonagh Added phenotypes Hepatic adenoma, somatic, 142330; Maturity-Onset Diabetes Of The Young; {Diabetes mellitus, insulin-dependent}, 222100; Renal cell carcinoma, 144700; Diabetes mellitus, insulin-dependent, 20, 612520; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3; MODY3; Maturity-onset diabetes of the young (MODY); {Diabetes mellitus, noninsulin-dependent, 2}, 125853; MODY, type III, 600496; Maturity Onset Diabetes of the Young for gene: HNF1A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.2 | HNF1A |
Ellen McDonagh gene: HNF1A was added gene: HNF1A was added to Monogenic diabetes. Sources: Expert Review Green Mode of inheritance for gene: HNF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: HNF1A were set to MODY, type III, 600496{Diabetes mellitus, noninsulin-dependent, 2}, 125853{Diabetes mellitus, insulin-dependent}, 222100Hepatic adenoma, somatic, 142330Renal cell carcinoma, 144700Diabetes mellitus, insulin-dependent, 20, 612520; Maturity Onset Diabetes of the Young |
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| Monogenic diabetes v0.2 | TRMT10A | Ellen McDonagh Added phenotypes failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies; young onset diabetes, short stature and microcephaly with intellectual disability for gene: TRMT10A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.2 | TRMT10A |
Ellen McDonagh gene: TRMT10A was added gene: TRMT10A was added to Monogenic diabetes. Sources: Expert Review Green Mode of inheritance for gene: TRMT10A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRMT10A were set to 26297882; 24204302 Phenotypes for gene: TRMT10A were set to failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies; young onset diabetes, short stature and microcephaly with intellectual disability |
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| Monogenic diabetes v0.2 | MNX1 | Ellen McDonagh Publications for gene MNX1 were changed from 24411943; Flanagan et al 2014 Cell Metab 19:146-154; 23562494; 26534984 to 24411943; 23562494; 26534984 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic diabetes v0.2 | MNX1 |
Ellen McDonagh gene: MNX1 was added gene: MNX1 was added to Monogenic diabetes. Sources: Expert Review Green Mode of inheritance for gene: MNX1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MNX1 were set to 24411943; Flanagan et al 2014 Cell Metab 19:146-154; 23562494; 26534984 |
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| Monogenic diabetes v0.2 | CEL |
Ellen McDonagh Added phenotypes Maturity-onset diabetes of the young, type VIII, 609812 for gene: CEL Publications for gene CEL were changed from PMID: 16369531 to 16369531 |
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| Monogenic diabetes v0.2 | CEL |
Ellen McDonagh gene: CEL was added gene: CEL was added to Monogenic diabetes. Sources: Expert Review Red Mode of inheritance for gene: CEL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CEL were set to PMID: 16369531 Phenotypes for gene: CEL were set to Maturity-onset diabetes of the young, type VIII, 609812 |
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