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| Cardiomyopathy_Paediatric v1.141 | FASTKD2 |
Richard Lin changed review comment from: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, structural cardiac morphology was not specifically commented by the authors. PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr). PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient. Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.; to: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, structural cardiac morphology was not specifically commented by the authors. PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr). PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C variant (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient. Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported. |
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| Cardiomyopathy_Paediatric v1.141 | FASTKD2 |
Richard Lin changed review comment from: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, cardiac morphology was not specifically commented by the authors. PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr). PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient. Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported.; to: PMID 31944455 reports 3 unrelated families with biallelic loss-of-function FASTKD2 variants causing mitochondrial disease; one family presented with childhood‑onset hypertrophic cardiomyopathy. A zebrafish knockdown model showed a decreased heart rate, structural cardiac morphology was not specifically commented by the authors. PMID: 39094958 reports an adult diagnosed with hypertrophic cardiomyopathy diagnosed at age 37, with CKD, found to be homozygous for a FASTDK2 missense variant c.29G>C p.(Ser10Thr). PMID: 38111113 reports a 39 year old patient with cardiomyopathy and nephropathy and a FASTKD2: c.29G>C (zygosity unknown), with the same authors as PMID: 39094958. Presumed to be the same patient. Current evidence is insufficient for diagnostic grade classification for paediatric cardiomyopathy because only a single family with paediatric cardiomyopathy is reported. |
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| Cardiomyopathy_Paediatric v1.135 | BRAF | Zornitza Stark Phenotypes for gene: BRAF were changed from Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150; syndromic HCM to Noonan syndrome, MONDO:0018997; cardiofaciocutaneous syndrome 1, MONDO:0007265 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v1.134 | BRAF | Zornitza Stark Publications for gene: BRAF were set to 19206169; 21396583 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v1.133 | BRAF | Zornitza Stark reviewed gene: BRAF: Rating: GREEN; Mode of pathogenicity: None; Publications: 37697378, 35770001, 35024745, 33274568, 30732632, 29704308, 29696744, 27569062; Phenotypes: Noonan syndrome, MONDO:0018997, cardiofaciocutaneous syndrome 1, MONDO:0007265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v1.0 | BRAF | Gene migrated from ENSG00000157764 to ENSG00000157764 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.210 | PRKAG2 | Zornitza Stark edited their review of gene: PRKAG2: Added comment: PMID 37013823 reports 3 infants from 2 unrelated families with biallelic truncating PRKAG2 variants presenting with severe neonatal dilated cardiomyopathy, rapid progression to cardiogenic shock and death. Homozygous p.Ile550Asnfs*58 identified in siblings; a 2504 bp exon 11 deletion causing frameshift identified in a third infant. Parents heterozygous and asymptomatic. Zebrafish double knockout model recapitulates reduced ejection fraction, ventricular thickening and atrial fibrillation, supporting loss‑of‑function disease mechanism.; Changed publications: 37013823; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.154 | ASNA1 |
Naomi Baker gene: ASNA1 was added gene: ASNA1 was added to Cardiomyopathy_Paediatric. Sources: Literature Mode of inheritance for gene: ASNA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASNA1 were set to 31461301; 16797549 Phenotypes for gene: ASNA1 were set to Dilated cardiomyopathy, MONDO:0001644, ASNA1-related Review for gene: ASNA1 was set to RED Added comment: Two siblings reported with biallelic variants - there were two variants on the paternal allele (c.867C>G p.(Cys289Trp) and c.913C>T p.(Gln305*)) and one variant on the maternal allele (c.488T>C p.(Val163Ala)). Unaffected sibling was heterozygous for maternal allele. Western blotting demonstrated reduced protein expression. Knockout of asna1 in zebrafish mode resulted in cardiac defects and early lethality. The Asna1 knockout mice displayed early embryonic lethality, consistent with a role of Asna1 in early embryonic development. Sources: Literature |
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| Cardiomyopathy_Paediatric v0.62 | MIB1 |
Ain Roesley changed review comment from: PMID: 30322850 4x probands - all missense except frameshift. All absent in gnomAD except for Ser520Arg (5 hets, 0 homs) Only W271G and the fs demonstrated reduced NOTCh signaling Mutant zebrafish were evaluated for degree of malformation Association with LVNC disputed by clingen - 2 variants reported in PMID: 23314057 however the missense has 45 hets and the nonsense has 13 hets. Clingen also pointed out that there's too many carriers of LoF variants in gnomAD for gene association to be real NO association with DCM by clingen; to: CHD: PMID: 30322850 4x probands - all missense except frameshift. All absent in gnomAD except for Ser520Arg (5 hets, 0 homs) Only W271G and the fs demonstrated reduced NOTCh signaling Mutant zebrafish were evaluated for degree of malformation Association with LVNC disputed by clingen - 2 variants reported in PMID: 23314057 however the missense has 45 hets and the nonsense has 13 hets. Clingen also pointed out that there's too many carriers of LoF variants in gnomAD for gene association to be real NO association with DCM by clingen |
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| Cardiomyopathy_Paediatric v0.60 | MIB1 |
Ain Roesley changed review comment from: PMID: 30322850 4x probands - all missense except frameshift. All absent in gnomAD except for Ser520Arg (5 hets, 0 homs) Only W271G and the fs demonstrated reduced NOTCh signaling Mutant zebrafish were evaluated for degree of malformation Associated with LVNC disputed by clingen NO association with DCM by clingen; to: PMID: 30322850 4x probands - all missense except frameshift. All absent in gnomAD except for Ser520Arg (5 hets, 0 homs) Only W271G and the fs demonstrated reduced NOTCh signaling Mutant zebrafish were evaluated for degree of malformation Association with LVNC disputed by clingen - 2 variants reported in PMID: 23314057 however the missense has 45 hets and the nonsense has 13 hets. Clingen also pointed out that there's too many carriers of LoF variants in gnomAD for gene association to be real NO association with DCM by clingen |
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| Cardiomyopathy_Paediatric v0.8 | BRAF | Zornitza Stark Marked gene: BRAF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.8 | BRAF | Zornitza Stark Gene: braf has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.8 | BRAF | Zornitza Stark Phenotypes for gene: BRAF were changed from Cardiofaciocutaneous Syndrome; LEOPARD Syndrome; Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150; syndromic HCM; Cardio-facio-cutaneous syndrome; LEOPARD syndrome 3; Noonan Syndrome; LEOPARD syndrome 3 613707 to Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150; syndromic HCM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiomyopathy_Paediatric v0.0 | BRAF |
Zornitza Stark gene: BRAF was added gene: BRAF was added to Cardiomyopathy_Paediatric. Sources: London South GLH,Expert List,Expert Review Green,NHS GMS,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 19206169; 21396583 Phenotypes for gene: BRAF were set to Cardiofaciocutaneous Syndrome; LEOPARD Syndrome; Noonan syndrome 7 613706; Cardiofaciocutaneous syndrome 115150; syndromic HCM; Cardio-facio-cutaneous syndrome; LEOPARD syndrome 3; Noonan Syndrome; LEOPARD syndrome 3 613707 Mode of pathogenicity for gene: BRAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments |
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