Paediatric or syndromic cardiomyopathy

Gene: BRAF

Green List (high evidence)

Comment on list classification: In a cohort of BRAF mutation-positive CFCS patients, pulmonic stenosis and hypertrophic cardiomyopathy were the most common cardiac defects, observed in approximately 90% and 55% of cases, respectively (PMID: 19206169 Sarkozy et al., 2014). As reviewed by Matthew Edwards, hypertrophic cardiomyopathy may also be the presenting feature in BRAF-related syndromes. Hence, this gene should be promoted to Green at the next GMS update.

Created: 21 Jan 2026, 1:33 p.m. | Last Modified: 21 Jan 2026, 1:33 p.m.

Panel Version: 7.92

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiofaciocutaneous syndrome, OMIM:115150

Publications

• 19206169

Green List (high evidence)

HCM common feature in BRAF-related Noonan/LEOPARD syndrome, and we have seen one case where HCM was the presenting feature, therefore appropriate for this panel

Created: 29 Dec 2025, 4:08 p.m. | Last Modified: 29 Dec 2025, 4:08 p.m.

Panel Version: 7.92

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 11:32 a.m. | Last Modified: 8 Mar 2022, 11:32 a.m.

Panel Version: 1.67

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.

Created: 2 Dec 2019, 3:58 p.m. | Last Modified: 2 Dec 2019, 3:58 p.m.

Panel Version: 0.16

I don't know

OMIM#211980; Adenocarcinoma of lung, somatic; OMIM#115150 Cardiofaciocutaneous syndrome; OMIM#613707 Colorectal cancer, somatic; OMIM#613707 LEOPARD syndrome 3; OMIM# Melanoma, malignant, somatic; Nonsmall cell lung cancer, somatic; OMIM#613706 Noonan syndrome 7.

Created: 25 Mar 2019, 4:30 p.m.

Rasopathy gene. HCM reported in Cardiofaciocutaneous syndrome and other heart defects in Leopard Syndrome.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

Comment on mode of pathogenicity: Missense variants are likely to be most relevant. Some variants found within Cardio-facio-cutaneous syndrome patients have been linked to gain-of-function, though some missense variants do not show increased BRAF activity in the publications. Reported as activating mutation consequence in G2P. Comments from reviewer: Gain of function mutations in BRAF cause Noonan syndrome, Cardio-Facio-cutanenous syndrome and LEOPARD syndrome. This disorders share phenotypes with Legius syndrome. - Helen Savage (Congenica Ltd), Jan. 22, 2016, 10:59 a.m. Gain of functions mutations in BRAF are reported to cause up to 2% of cases of Noonan syndrome. - Helen Savage (Congenica Ltd), Jan. 21, 2016, 11:48 a.m.

Created: 5 Feb 2016, 12:04 p.m.

Comment when marking as ready: This gene was promoted to green, as it has a strong evidence of being indicated in Noonan syndrome, LEOPARD syndrome and Cardio-facio-cutaneous syndrome, and as phenotypes are often difficult to distinguish, this gene should also be examined in patients recruited under the other rasopathy syndromes. This gene is part of the eligibility criteria for prior genetic testing of rasopathy patients.

Created: 4 Feb 2016, 3:33 p.m.

Green List (high evidence)

Gain of function mutations

Created: 27 Jan 2016, 4 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Noonan syndrome; LEOPARD syndrome; Cardio-facio-cutaneous syndrome

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments