Atrial Fibrillation

Gene: NPPA

I don't know

PMID: 36303204:
- 1x Brugada patient with heterozygous R107X (NMD-predicted, 5 hets in gnomADv3), regarded as ACMG-LP.

PMID: 19646991:
- NPPA S64R missense in one fam with familial AF, heterozygous in two affected family members but was absent in unaffected family members and their controls. This variant has 195 hets in gnomADv3.

PMID: 23275345:
- Segregation of the homozygous p.R150Q mutation of the NPPA gene with the phenotype in the 6 families with autosomal recessive AD cardiomyopathy (ADCM). This variant has no homozygotes in gnomAD.

ClinGen gene curation: for autosomal recessive DCM - No Known Disease Relationship (09/04/2020).

Created: 5 Apr 2023, 7:48 a.m. | Last Modified: 5 Apr 2023, 7:48 a.m.

Panel Version: 1.1

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Atrial fibrillation, familial, 6 (MIM#612201), AD; Atrial standstill 2 (MIM#615745), AR

Publications

• 36303204
• 19646991
• 23275345

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

Comment when marking as ready: Two families and functional data, including animal models but note AF is relatively common and generally multifactorial so more evidence would be desirable for Green rating.

Created: 3 Dec 2020, 2:50 a.m. | Last Modified: 3 Dec 2020, 2:50 a.m.

Panel Version: 0.6

I don't know

PMID: 18614783;
- 1x family with 11 affecteds heterozygous for a frameshift, which leads to a longer mature protein
- isolated heart model demonstrated significant shortening of the monophasic action potential (MAP) duration and the effective refractory period

PMID: 31077706;
- mouse model of the frameshift mentioned above, which were more prone to developing to AF

PMID: 31034774;
- In vitro studies and rat model of a missense identified in an earlier study PMID 20064500
- Noted that the animals were more susceptible to AF compared to WT
- classified it as LP based on ACMG

Created: 26 Nov 2020, 12:54 a.m. | Last Modified: 26 Nov 2020, 12:54 a.m.

Panel Version: 0.2

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Atrial fibrillation, familial, 6, (MIM#612201)

Publications

• 18614783
• 20064500
• 31034774
• 31077706