Hypertrophic cardiomyopathy

Gene: LZTR1

Red List (low evidence)

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

Red List (low evidence)

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

• 30732632

Red List (low evidence)

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 panel

Created: 18 Sep 2019, 12:50 p.m. | Last Modified: 18 Sep 2019, 12:50 p.m.

Panel Version: 1.74

Publications

• 30732632

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.

Green List (high evidence)

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: Literature

Created: 13 Feb 2019, 8:39 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
RASopathy-associated cardiomyopathy

Publications

• 30368668
• 30732632