Hypertrophic cardiomyopathy
Gene: LZTR1
Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be demoted from Green to Red as this is a RASopathy gene and should not be included here.Created: 2 Dec 2019, 11:26 a.m. | Last Modified: 2 Dec 2019, 11:26 a.m.
Panel Version: 1.81
Gene not currently tested on Manchester cardiac gene panel. 112 variants listed on HGMD (accessed 19/09/2019). ClinGen Knowledge Base: limited association with Noonan syndrome (accessed 19/09/2019).Created: 19 Sep 2019, 10:09 a.m. | Last Modified: 19 Sep 2019, 10:09 a.m.
Panel Version: 1.74
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Noonan syndrome 10 (616564); Noonan syndrome 2 (605275)
Publications
This is not on the CGGL Royal Brompton diagnostic panel. HCM is a feature of RASopathies, but there is no evidence that variants in this gene would cause isolated/later onset HCM. No other RASopathy genes are reviewed as Green on this panel, therefore this gene would seem more appropriate for a distinct RASopathy panelCreated: 18 Sep 2019, 12:50 p.m. | Last Modified: 18 Sep 2019, 12:50 p.m.
Panel Version: 1.74
Publications
Comment on list classification: Promoted from Red to Green due to new review from Anna De Burca, and clinical advise that this gene would be suitable to include on this panel.Created: 25 Feb 2019, 11:32 a.m.
PMID:30368668 describes the clinical phenotype of 7 unrelated patients with Noonan or Noonan-like syndrome associated with monoallelic or biallelic variants in LZTR1. Five of the patients (one with biallelic variants and four with monoallelic variants) had hypertrophic cardiomyopathy. PMID:30732632 describes the phenotype in 46 unrelated children with RASopathy derived from a cohort of 168 paediatric HCM patients. One of the 46 children with RASopathy had compound heterozygous missense variants in LZTR1, although it is unclear whether this gene was tested in all participants, as it was not included in the exome-based 'expanded cardiomyopathy' panel applied. Given the phenotypic variability of Noonan syndrome, it seems plausible that mild cases could present with apparently isolated hypertrophic cardiomyopathy.
Sources: LiteratureCreated: 13 Feb 2019, 8:39 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
RASopathy-associated cardiomyopathy
Publications
Source Expert Review Red was added to LZTR1. Rating Changed from Green List (high evidence) to Red List (low evidence)
Gene: lztr1 has been classified as Green List (High Evidence).
gene: LZTR1 was added gene: LZTR1 was added to Hypertrophic cardiomyopathy - teen and adult. Sources: Literature Mode of inheritance for gene: LZTR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: LZTR1 were set to 30368668; 30732632 Phenotypes for gene: LZTR1 were set to RASopathy-associated cardiomyopathy Review for gene: LZTR1 was set to GREEN