NM_001038.6(SCNN1A):c.1449del (p.Tyr484fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 4, 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:: RCV001579849.5

Allele description [Variation Report for NM_001038.6(SCNN1A):c.1449del (p.Tyr484fs)]

NM_001038.6(SCNN1A):c.1449del (p.Tyr484fs)

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.1449del (p.Tyr484fs)

HGVS:

NC_000012.12:g.6349212del
NG_011945.2:g.33146del
NM_001038.6:c.1449delMANE SELECT
NM_001159575.2:c.1518del
NM_001159576.2:c.1626del
NP_001029.1:p.Tyr484fs
NP_001153047.1:p.Tyr507fs
NP_001153048.1:p.Tyr543fs
NC_000012.11:g.6458378del
NM_001038.5:c.1449delC

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

Y484fs

Links:

OMIM: 600228.0003; dbSNP: rs756434927

Molecular consequence:

NM_001038.6:c.1449del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159575.2:c.1518del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159576.2:c.1626del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001808732	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001957649	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV004295829	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 4, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10403853, 23416952, 10586178, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001808732

Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV001957649

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV004295829

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 4, 2024)

germline

clinical testing

PubMed (4)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	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

Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1.

Welzel M, Akin L, Büscher A, Güran T, Hauffa BP, Högler W, Leonards J, Karges B, Kentrup H, Kirel B, Senses EE, Tekin N, Holterhus PM, Riepe FG.

Eur J Endocrinol. 2013 Apr 15;168(5):707-15. doi: 10.1530/EJE-12-1000. Print 2013 May.

PubMed [citation]

PMID:: 23416952

See all PubMed Citations (4)

Details of each submission

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001808732.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001957649.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295829.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Tyr484Thrfs*13) in the SCNN1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCNN1A are known to be pathogenic (PMID: 10403853, 23416952). This variant is present in population databases (rs756434927, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with pseudohypoaldosteronism type 1 (PMID: 10586178). ClinVar contains an entry for this variant (Variation ID: 9265). For these reasons, this variant has been classified as Pathogenic.

#	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: Apr 12, 2026

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