Paediatric or syndromic cardiomyopathy

Gene: NF1

Green List (high evidence)

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

Created: 11 Mar 2026, 2:06 p.m. | Last Modified: 11 Mar 2026, 2:06 p.m.

Panel Version: 7.98

Green List (high evidence)

Comment on list classification: There are three unrelated patients reported with monoallelic NF1 gene deletions and hypertrophic cardiomyopathy. In addition, three patients were reported with monoallelic NF1 small variants and cardiomyopathy.

Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 29 Aug 2025, 7:55 p.m. | Last Modified: 29 Aug 2025, 7:55 p.m.

Panel Version: 7.46

Comment on phenotypes: OMIM phenotypes accessed on 29 August 2025.

Created: 29 Aug 2025, 7:51 p.m. | Last Modified: 29 Aug 2025, 7:51 p.m.

Panel Version: 7.45

PMID: 23278345 (2013) reported 16 patients with large 1.4Mb NF1 deletions (autosomal dominant and mostly de novo) and 16 age- and sex-matched NF1 patients without such deletions. Six of 16 NF1 deletion patients but none of 16 non-deletion NF1 patients had major cardiac abnormalities. Three of deletion patients had hypertrophic cardiomyopathy.

PMID:30919579 (2019) reported the first published case of foetal hypertrophic cardiomyopathy and the patient was identified with a novel pathogenic heterozygous variant in NF1 gene (c.7858_7859delGA/ p.Glu2620IlefsX18). This variant is predicted to cause loss of normal protein function and was not identified in large population cohorts, as discussed in this publication.

PMID:38654147 (2024) reported a 20-year-old male patient of Iranian descent with neurofibromatosis type I, who presented with clinical manifestations consistent with arrhythmogenic cardiomyopathy. The patient was identified with likely pathogenic heterozygous missense variant in NF1 gene (c.3277G > A/ p.Val1093Met). The patient’s parents and brother that didn’t show any symptoms of NF1 did not harbour the variant.

PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one patient with dilated cardiomyopathy was identified with a heterozygous pathogenic stop-gain variant in NF1 gene (c.5305C>T/ p.Arg1769Ter).

Created: 29 Aug 2025, 7:46 p.m. | Last Modified: 29 Aug 2025, 7:46 p.m.

Panel Version: 7.43

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurofibromatosis, type 1, OMIM:162200; Neurofibromatosis, familial spinal, OMIM:162210; Neurofibromatosis-Noonan syndrome, OMIM:601321; Watson syndrome, OMIM:193520; cardiomyopathy, MONDO:0004994

Publications

• 23278345
• 30919579
• 38654147
• 39472908

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

Comment on list classification: Is a confirmed DD gene for neurofibromatosis-noonan syndrome and neurofibromatosis type 1. Comment from Reviewer: Shares overlapping features with Noonan syndrome.
Helen Savage (Congenica Ltd), Jan. 27, 2016, 3:18 p.m.

Created: 5 Feb 2016, 12:53 p.m.

Comment on mode of inheritance: Confirmed on G2P and OMIM, and not on imprinted gene list.

Created: 5 Feb 2016, 9:14 a.m.

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurofibromatosis syndrome 1