Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
18 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.92 | BRAF | Eleanor Williams Tag Q1_26_NHS_review tag was added to gene: BRAF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.92 | BRAF | Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: BRAF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.92 | BRAF | Ida Ertmanska reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: None; Publications: 19206169; Phenotypes: Cardiofaciocutaneous syndrome, OMIM:115150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.92 | BRAF | Matthew Edwards reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.86 | PKD2 | Achchuthan Shanmugasundram Added comment: Comment on list classification: There are patients from five unrelated families reported with five different heterozygous PKD2 variants and with cardiomyopathy. Of these, four families were from APKD2 database at Mayo Clinic and one was from the UK 100,000 genomes cohort. There is also functional evidence available from zebrafish and mice model. Hence, this gene can be promoted to green rating in the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.85 | PKD2 |
Achchuthan Shanmugasundram changed review comment from: Autosomal dominant variants in PKD2 gene are associated with Polycystic kidney disease 2 (MIM #613095, OMIM phenotype accessed on 07 September 2025). Reports on human patients: PMID:23376035 (2014) examined ADPKD database at Mayo clinic with 2,620 ADPKD patients seen between 1984 and 2010, where 374 patients were genotyped and 67 of them were identified with PKD2 variants. Of these 67, six patients from four different families had a diagnosis of idiopathic dilated cardiomyopathy (IDCM). The identified variants were p.Arg361Ter, p.Arg807Ter, c.423_430del8 and c.1095-5A>G. PMID:29270497 (2017) reported 3,885 ADPKD patients seen in the period between 1984 and 2015 in the same database as PMID:23376035, of which seven patients from four families had the same PKD2 variants. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one adult male patient with hypertrophic cardiomyopathy was identified with a heterozygous stop-gain variant in PKD2 gene via analysis of data from singleton genome sequencing. Functional studies: PMID:23376035 (2014) studied Pkd2 mutant zebrafish, which showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. PMID:27081851 (2016) reported that 9-month-old Pkd2+/- mice showed several anatomical features consistent with a dilated cardiac phenotype. However, Pkd2+/- 5-month-old mice did not present with a cardiac phenotype that paralleled either dilated cardiomyopathy or left ventricular hypertrophy, suggesting that PKD2 caused late-onset progressive cardiomyopathy. Sources: Literature; to: Autosomal dominant variants in PKD2 gene are associated with Polycystic kidney disease 2 (MIM #613095, OMIM phenotype accessed on 07 September 2025). Reports on human patients: PMID:23376035 (2014) examined ADPKD database at Mayo clinic with 2,620 ADPKD patients seen between 1984 and 2010, where 374 patients were genotyped and 67 of them were identified with PKD2 variants. Of these 67, six patients from four different families had a diagnosis of idiopathic dilated cardiomyopathy (IDCM). The identified variants were p.Arg361Ter, p.Arg807Ter, c.423_430del8 and c.1095-5A>G. PMID:29270497 (2017) reported 3,885 ADPKD patients seen in the period between 1984 and 2015 in the same database as PMID:23376035, of which seven patients from four families had the same PKD2 variants. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one adult male patient with hypertrophic cardiomyopathy was identified with a heterozygous stop-gain variant in PKD2 gene (p.Arg213Ter) via analysis of data from singleton genome sequencing. Functional studies: PMID:23376035 (2014) studied Pkd2 mutant zebrafish, which showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. PMID:27081851 (2016) reported that 9-month-old Pkd2+/- mice showed several anatomical features consistent with a dilated cardiac phenotype. However, Pkd2+/- 5-month-old mice did not present with a cardiac phenotype that paralleled either dilated cardiomyopathy or left ventricular hypertrophy, suggesting that PKD2 caused late-onset progressive cardiomyopathy. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.85 | PKD2 |
Achchuthan Shanmugasundram gene: PKD2 was added gene: PKD2 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature Mode of inheritance for gene: PKD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PKD2 were set to 23376035; 27081851; 29270497; 39472908 Phenotypes for gene: PKD2 were set to Polycystic kidney disease 2, OMIM:613095; polycystic kidney disease 2, MONDO:0013131; dilated cardiomyopathy, MONDO:0005021 Review for gene: PKD2 was set to GREEN Added comment: Autosomal dominant variants in PKD2 gene are associated with Polycystic kidney disease 2 (MIM #613095, OMIM phenotype accessed on 07 September 2025). Reports on human patients: PMID:23376035 (2014) examined ADPKD database at Mayo clinic with 2,620 ADPKD patients seen between 1984 and 2010, where 374 patients were genotyped and 67 of them were identified with PKD2 variants. Of these 67, six patients from four different families had a diagnosis of idiopathic dilated cardiomyopathy (IDCM). The identified variants were p.Arg361Ter, p.Arg807Ter, c.423_430del8 and c.1095-5A>G. PMID:29270497 (2017) reported 3,885 ADPKD patients seen in the period between 1984 and 2015 in the same database as PMID:23376035, of which seven patients from four families had the same PKD2 variants. PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one adult male patient with hypertrophic cardiomyopathy was identified with a heterozygous stop-gain variant in PKD2 gene via analysis of data from singleton genome sequencing. Functional studies: PMID:23376035 (2014) studied Pkd2 mutant zebrafish, which showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. PMID:27081851 (2016) reported that 9-month-old Pkd2+/- mice showed several anatomical features consistent with a dilated cardiac phenotype. However, Pkd2+/- 5-month-old mice did not present with a cardiac phenotype that paralleled either dilated cardiomyopathy or left ventricular hypertrophy, suggesting that PKD2 caused late-onset progressive cardiomyopathy. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.15 | FLII |
Achchuthan Shanmugasundram changed review comment from: PMID:32870709 (2020) reported a large cohort of 205 unrelated patients with various forms of childhood-onset cardiomyopathy (CM), in which two unrelated patients of Saudi Arabian decent with infantile-onset dilated CM were identified with homozygous missense variants (p.Leu674Val & p.Arg1240Cys). PMID:37561591 (2023) identified biallelic variants in FLII gene in three unrelated families with idiopathic, early-onset dilated CM of which two patients were the ones that were already reported in PMID:32870709. The third patient was a girl of Dutch decent that had onset of CM at around 2 months of age. This patient was identified with compound heterozygous variants (p.Gln454Ter & p.Arg1168Trp). Introduction of patient-specific FLII variants into the zebrafish genome using CRISPR/Cas9 genome editing resulted in the manifestation of key aspects of morphological and functional abnormalities of the heart, as observed in the patients. In addition, functional studies also provided insights into the function of Flii during ventricular chamber morphogenesis that involves myocardial cell adhesion and myofibril organisation. This gene has been associated with dilated CM phenotype in OMIM (MIM #620635).; to: PMID:32870709 (2020) reported a large cohort of 205 unrelated patients with various forms of childhood-onset cardiomyopathy (CM), in which two unrelated patients of Saudi Arabian descent with infantile-onset dilated CM were identified with homozygous missense variants (p.Leu674Val & p.Arg1240Cys). PMID:37561591 (2023) identified biallelic variants in FLII gene in three unrelated families with idiopathic, early-onset dilated CM of which two patients were the ones that were already reported in PMID:32870709. The third patient was a girl of Dutch descent that had onset of CM at around 2 months of age. This patient was identified with compound heterozygous variants (p.Gln454Ter & p.Arg1168Trp). Introduction of patient-specific FLII variants into the zebrafish genome using CRISPR/Cas9 genome editing resulted in the manifestation of key aspects of morphological and functional abnormalities of the heart, as observed in the patients. In addition, functional studies also provided insights into the function of Flii during ventricular chamber morphogenesis that involves myocardial cell adhesion and myofibril organisation. This gene has been associated with dilated CM phenotype in OMIM (MIM #620635). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v7.9 | ASNA1 |
Achchuthan Shanmugasundram changed review comment from: As reviewed by Dmitrijs Rots, PMID:31461301 reported the identification of compound heterozygous variants in two siblings with early infantile-onset, rapidly progressive dilated cardiomyopathy. There were two variants reported on the paternal allele (p.Cys289Trp and p.Gln305Ter) and one variant on the maternal allele (p.Val163Ala). Unaffected sibling was heterozygous for maternal allele. Functional studies showed that Val163Ala variant leads to protein misfolding as well as less effective tail-anchored protein insertion. Loss of asna1 in zebrafish resulted in reduced cardiac contractility and early lethality. In contrast to wild-type mRNA, injection of either mutant mRNA failed to rescue this phenotype. As there is only one case and functional evidence available in support of this association, this gene can only be rated amber now.; to: PMID:31461301 reported the identification of compound heterozygous variants in two siblings with early infantile-onset, rapidly progressive dilated cardiomyopathy. There were two variants reported on the paternal allele (p.Cys289Trp and p.Gln305Ter) and one variant on the maternal allele (p.Val163Ala). Unaffected sibling was heterozygous for maternal allele. Functional studies showed that Val163Ala variant leads to protein misfolding as well as less effective tail-anchored protein insertion. Loss of asna1 in zebrafish resulted in reduced cardiac contractility and early lethality. In contrast to wild-type mRNA, injection of either mutant mRNA failed to rescue this phenotype. As there is only one case and functional evidence available in support of this association, this gene can only be rated amber now. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v5.7 | TAF1A | Sarah Leigh edited their review of gene: TAF1A: Added comment: Biallelic TAF1A variants have been associated with dilated cardiomyopathy. To date, five missense TAF1A variants and a 1.62Mb deletion (that includes the TAF1A gene) have been reported in three unrelated cases of childhood dilated cardiomyopathy (PMIDs 28472305; 29367541; 37501913, personal communication from Genomics Clinical Fellow). The unaffected parents of these cases were all heterozygous for the relevant TAF1A variant. A stable knockout of the single taf1a zebrafish homolog, was used to generate homozygous embryos, which mirrored the heart failure phenotype beginning at 6 days post-fertilization (PMID: 28472305).; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v1.67 | BRAF | Ivone Leong commented on gene: BRAF: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v1.66 | BRAF |
Ivone Leong Source Expert Review Amber was added to BRAF. Rating Changed from Green List (high evidence) to Amber List (moderate evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v1.53 | KIF20A | Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. PMID: 29357359 describes 1 family with 2 affect sibs. The authors also made a zebrafish MO model, which had a progressive cardiac phenotype starting at 48 hpf. Currently, there is insufficient evidence to support a gene-disease association. Therefore this gene has been given a Red rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v1.38 | NRAP |
Ivone Leong gene: NRAP was added gene: NRAP was added to Cardiomyopathies - including childhood onset. Sources: Literature Q2_21_rating tags were added to gene: NRAP. Mode of inheritance for gene: NRAP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NRAP were set to 30384889; 33534821; 28611399; https://doi.org/10.1101/2020.10.12.20211474; 32870709 Phenotypes for gene: NRAP were set to Dilated cardiomyopathy, MONDO:0005021 Edit Review for gene: NRAP was set to GREEN Added comment: This gene is Green on the Dilated cardiomyopathy - adult and teen (Version 1.22) with the following reviews: "This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There are >3 unrelated cases of patients with variants in this gene and having DCM. https://doi.org/10.1101/2020.10.12.20211474 also describes a CRISPR knockout zebrafish which had a cardiac phenotype. Therefore, there is enough evidence to support a gene-disease association and this gene is recommended to be promoted Green at the next panel review. Sources: Literature Ivone Leong (Genomics England Curator), 25 Feb 2021" "Twenty unrelated families reported with childhood onset DCM. May be more appropriate for the paediatric cardiomyopathy panel." As affected individuals have childhood onset DCM it was deemed appropriate to add this gene to this panel as well. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.16 | BRAF | Ivone Leong reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.15 | BRAF | Ivone Leong Source NHS GMS was added to BRAF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.4 | BRAF |
Ivone Leong Source Expert List was added to BRAF. Mode of pathogenicity for gene BRAF was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Added phenotypes Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150; LEOPARD syndrome 3 613707 for gene: BRAF Publications for gene BRAF were changed from 21396583; PMID: 19206169 to 21396583; 19206169 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.1 | BRAF |
Ivone Leong gene: BRAF was added gene: BRAF was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,London South GLH,South West GLH Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BRAF were set to 21396583; PMID: 19206169 Phenotypes for gene: BRAF were set to Noonan Syndrome; syndromic HCM; LEOPARD syndrome 3; LEOPARD Syndrome; Cardio-facio-cutaneous syndrome; Cardiofaciocutaneous Syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||