Dilated and arrhythmogenic cardiomyopathy
Gene: MYZAPComment on list classification: New gene added to the panel by Aleš Maver. MYZAP is not yet associated with any phenotype in OMIM or Gene2Phenoype. At least three unrelated families have been reported with biallelic LOF variants in MYZAP and a phenotype of DCM (PMIDs: 34899865; 35840178; 38436102). Studies in zebrafish and mice demonstrate the link between MYZAP and cardiomyopathy (PMIDs: 20093627; 24698889). Overall, the evidence is sufficient to promote this gene to Green at the next GMS panel update.Created: 17 Apr 2024, 9:47 a.m. | Last Modified: 17 Apr 2024, 9:47 a.m.
Panel Version: 2.21
Comment on mode of pathogenicity: Changed from "Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments" to "Other". LOF does cause phenotype.Created: 16 Aug 2022, 12:41 p.m. | Last Modified: 16 Aug 2022, 12:41 p.m.
Panel Version: 1.30
Two independent publications reported the presence of biallelic loss-of-function variants in MYZAP gene in three families altogether with recessive dilated cardiomyopathy (DCM) (PMID:34899865 and PMID:35840178). Altogether, 8 patients with DCM and biallelic LOF variants are reported in the three published families.
Functional studies published previously linked the loss of MYZAP protein to DCM in zebrafish (PMID:20093627).
Functional studies of the variant reported in PMID:35840178 have shown that the variant led to lower force and longer time to peak contraction and relaxation consistent with severe contractile dysfunction in the patient-derived iPSC cardiomyocytes.
Sources: OtherCreated: 11 Aug 2022, 8:32 a.m. | Last Modified: 11 Aug 2022, 8:39 a.m.
Panel Version: 1.28
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Dilated cardiomyopathy
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Tag Q2_24_promote_green tag was added to gene: MYZAP.
Publications for gene: MYZAP were set to 34899865; 20093627; 35840178
Gene: myzap has been classified as Amber List (Moderate Evidence).
Gene: myzap has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MYZAP were changed from Dilated cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021
Mode of pathogenicity for gene: MYZAP was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Other
Publications for gene: MYZAP were set to 34899865; doi:10.1101/mcs.a006221
gene: MYZAP was added gene: MYZAP was added to Dilated cardiomyopathy - adult and teen. Sources: Other Mode of inheritance for gene: MYZAP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYZAP were set to 34899865; doi:10.1101/mcs.a006221 Phenotypes for gene: MYZAP were set to Dilated cardiomyopathy Penetrance for gene: MYZAP were set to unknown Mode of pathogenicity for gene: MYZAP was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: MYZAP was set to RED