NM_001038.6(SCNN1A):c.942del (p.Asn315fs) AND Idiopathic bronchiectasis

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 20, 2016
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:: RCV000614949.4

Allele description [Variation Report for NM_001038.6(SCNN1A):c.942del (p.Asn315fs)]

NM_001038.6(SCNN1A):c.942del (p.Asn315fs)

Gene:

SCNN1A:sodium channel epithelial 1 subunit alpha [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12p13.31

Genomic location:

Preferred name:

NM_001038.6(SCNN1A):c.942del (p.Asn315fs)

HGVS:

NC_000012.12:g.6355815del
NG_011945.2:g.26544del
NM_001038.6:c.942delMANE SELECT
NM_001159575.2:c.1011del
NM_001159576.2:c.1119del
NP_001029.1:p.Asn315fs
NP_001153047.1:p.Asn338fs
NP_001153048.1:p.Asn374fs
NC_000012.11:g.6464980delG
NC_000012.11:g.6464981del
NM_001159576.1:c.1119delC
p.Asn374ThrfsX16

Protein change:

N315fs

Links:

dbSNP: rs1555112332

NCBI 1000 Genomes Browser:

rs1555112332

Molecular consequence:

NM_001038.6:c.942del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159575.2:c.1011del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159576.2:c.1119del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Idiopathic bronchiectasis
Identifiers:: MONDO: MONDO:0018956; MedGen: C0339985

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000712035	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (May 20, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10403853, 23392097, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000712035

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(May 20, 2016)

germline

clinical testing

PubMed (3)
[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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudohypoaldosteronism.

Kerem E, Bistritzer T, Hanukoglu A, Hofmann T, Zhou Z, Bennett W, MacLaughlin E, Barker P, Nash M, Quittell L, Boucher R, Knowles MR.

N Engl J Med. 1999 Jul 15;341(3):156-62.

PubMed [citation]

PMID:: 10403853

Pseudohypoaldosteronism.

Riepe FG.

Endocr Dev. 2013;24:86-95. doi: 10.1159/000342508. Epub 2013 Feb 1. Review.

PubMed [citation]

PMID:: 23392097

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000712035.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The p.Asn374fs variant in SCNN1A has not been previously reported in individuals with pulmonary disease or in large population studies. This variant is predicte d to cause a frameshift, which alters the protein?s amino acid sequence beginnin g at position 374 and leads to a premature termination codon 16 amino acids down stream. This alteration is then predicted to lead to a truncated or absent prote in. Heterozygous loss of function of the SCNN1A gene is an established disease m echanism in individuals with pseudohypoaldosteronism which can include a pulmona ry phenotype. In summary, although additional studies are required to fully esta blish its clinical significance, the p.Asn374fs variant is likely pathogenic.

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

Last Updated: Dec 24, 2022

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