NM_006172.4(NPPA):c.449G>A (p.Arg150Gln) AND Atrial fibrillation, familial, 6

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 13, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001344090.5

Allele description [Variation Report for NM_006172.4(NPPA):c.449G>A (p.Arg150Gln)]

NM_006172.4(NPPA):c.449G>A (p.Arg150Gln)

Genes:

NPPA-AS1:NPPA antisense RNA 1 [Gene - HGNC]
LOC114827827:VISTA enhancer hs2123 [Gene]
NPPA:natriuretic peptide A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_006172.4(NPPA):c.449G>A (p.Arg150Gln)

HGVS:

NC_000001.11:g.11847114C>T
NG_012926.1:g.5670G>A
NG_065183.1:g.396C>T
NM_006172.4:c.449G>AMANE SELECT
NP_006163.1:p.Arg150Gln
LRG_751t1:c.449G>A
LRG_751:g.5670G>A
NC_000001.10:g.11907171C>T
NM_006172.3:c.449G>A

Protein change:

R150Q; ARG150GLN

Links:

OMIM: 108780.0003; dbSNP: rs202102042

NCBI 1000 Genomes Browser:

rs202102042

Molecular consequence:

NM_006172.4:c.449G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atrial fibrillation, familial, 6 (ATFB6)
Identifiers:: MONDO: MONDO:0012816; MedGen: C2677294; OMIM: 612201

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001538126	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 13, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23275345, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001538126

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 13, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A.

Disertori M, Quintarelli S, Grasso M, Pilotto A, Narula N, Favalli V, Canclini C, Diegoli M, Mazzola S, Marini M, Del Greco M, Bonmassari R, Masè M, Ravelli F, Specchia C, Arbustini E.

Circ Cardiovasc Genet. 2013 Feb;6(1):27-36. doi: 10.1161/CIRCGENETICS.112.963520. Epub 2012 Dec 29.

PubMed [citation]

PMID:: 23275345

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001538126.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 150 of the NPPA protein (p.Arg150Gln). This variant is present in population databases (rs202102042, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of autosomal recessive atrial dilated cardiomyopathy (PMID: 23275345). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 126846). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine