Familial non syndromic congenital heart disease
Gene: MYH6Comment on mode of inheritance: MOI change dfrom "BIALLELIC, autosomal or pseudoautosomal" to "Both Monoallelic and Biallelic" as Monoallelic variants also cause disease.Created: 18 Mar 2022, 12:44 p.m. | Last Modified: 18 Mar 2022, 12:44 p.m.
Panel Version: 1.75
Comment on list classification: Discussed internally with Arianna Tucci (Genomics England Clinical Team), and enough evidence for biallelic variants causing Shone complex. Promoted from Amber to Green due to this feedback.Created: 18 Dec 2017, 3:17 p.m.
PMID: 28991257 - a new publication reports seven rare damaging recessive genotypes in this gene in 7 patients with cardiac heart disease from the NHLBI Pediatric Cardiac Genomics Consortium cohort. These include predicted loss-of-function and missense variants. They compared the observed number of rare damaging recessive genotypes to the expected frequency, estimated from the de novo probability and adjusting for consanguinity. They state that recessive genotypes in MYH6 accounted for 11% of the 37 sequenced patients with Shone complex. "Patients with Shone complex and biallelic MYH6 mutations may be at particular risk for ventricular dysfunction, potentially allowing early identification and intervention". It is unclear whether the variants segregated in the family with disease, or if these were the only candidate variants identified in these patients.Created: 18 Oct 2017, 10:25 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Shone complex
Publications
Large family reported to date, with ASD.Created: 4 Jul 2017, 7:24 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Atrial septal defect; Atrial septal defect 3, 614089
Publications
Known to cause cardiomyopathy. Also reported in ASD and other congenital heart disease patients but with decreased penetranceCreated: 28 Nov 2016, 4:35 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Phenotypes
Atrial septal defect 3 614089
Publications
Mode of inheritance for gene: MYH6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYH6 were set to 15735645, 20656787
Phenotypes for MYH6 were set to Atrial septal defect 3 614089; Shone complex
This gene has been classified as Green List (High Evidence).
Mode of inheritance for MYH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to BIALLELIC, autosomal or pseudoautosomal
Promoted to version 1 by Alice Gardham on 26th January
MYH6 was created by agardham
MYH6 was added to Familial non syndromic congenital heart diseasepanel. Sources: Illumina TruGenome Clinical Sequencing Services,Literature,Radboud University Medical Center, Nijmegen