Paediatric or syndromic cardiomyopathy

Gene: NAA15

I don't know

Just adding more cases for review- 2 more cases in patient with HCM (both GMS WGS cases, both in CVA, one from our lab in patient presenting with HCM (de novo), another with HCM as HPO term in CVA). Evidence is still fairly limited, as HCM seems rare, so this small number may stll be chance.

Created: 3 Feb 2026, 10:15 a.m. | Last Modified: 3 Feb 2026, 10:15 a.m.

Panel Version: 7.93

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypertrophic cardiomyopathy

I don't know

Comment on list classification: The majority of the cases reported with heterozygous NAA15 variants do not present with cardiomyopathy, while a significant proportion of cases had congenital cardiac defects.

There were >50 cases reported in total. However, only three unrelated cases were reported with cardiomyopathy (two frameshift variants and one missense variant), of which one of the cases were from the UK 100,000 genomes project cohort.

Hence, this gene should remain as amber. The 'watchlist' tag has been added to review new evidence in the future.

Created: 29 Aug 2025, 6:01 p.m. | Last Modified: 29 Aug 2025, 6:01 p.m.

Panel Version: 7.43

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

Created: 29 Aug 2025, 5:52 p.m. | Last Modified: 29 Aug 2025, 5:52 p.m.

Panel Version: 7.42

PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one patient with hypertrophic cardiomyopathy was identified with heterozygous frameshift variant in NAA15 gene (c.174_177del/ p.Cys58TrpfsTer15). Only the patient genome was sequenced.

Created: 29 Aug 2025, 5:50 p.m. | Last Modified: 29 Aug 2025, 6:02 p.m.

Panel Version: 7.43

Comment on gene rating: The rating of this gene should remain amber in this panel, as there are only two unrelated cases reported with paediatric hypertrophic cardiomyopathy.

PMID:33103328 reported two unrelated individuals with paediatric hypertrophic cardiomyopathy and they were identified with de novo variants in NAA15 gene (patient 1: c.1009_1012delGAAA/ p.Glu337fs, patient 2: c.79A>G/ p.Arg27Gly). These patients presented with cardiomyopathy at 2 months and 6 years of age respectively.

Although none of the patients were reported with hypertrophic cardiomyopathy in PMID:29656860, 4 of 19 patients were reported with congenital cardiac defects.

Although this gene has not yet been associated with cardiac abnormalities in OMIM, this gene has been associated with "Congenital heart disease and neurodevelopmental disorder" in the DD panel of Gene2Phenotype database (with 'strong' rating).

Created: 31 Jul 2023, 9:40 a.m. | Last Modified: 29 Aug 2025, 5:39 p.m.

Panel Version: 7.40

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
hypertrophic cardiomyopathy, MONDO:0005045

Publications

• 33103328
• 39472908

I don't know

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

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

Panel Version: 0.16