NM_000335.5(SCN5A):c.5248TTC[1] (p.Phe1751del) AND Brugada syndrome 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 1, 2022
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:: RCV002300646.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.5248TTC[1] (p.Phe1751del)]

NM_000335.5(SCN5A):c.5248TTC[1] (p.Phe1751del)

Gene:

SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.5248TTC[1] (p.Phe1751del)

HGVS:

NC_000003.12:g.38551118AGA[1]
NG_008934.1:g.103552TTC[1]
NM_000335.5:c.5248TTC[1]MANE SELECT
NM_001099404.2:c.5251TTC[1]
NM_001099405.2:c.5197TTC[1]
NM_001160160.2:c.5152TTC[1]
NM_001160161.2:c.5089TTC[1]
NM_001354701.2:c.5194TTC[1]
NM_198056.3:c.5251TTC[1]
NP_000326.2:p.Phe1751del
NP_001092874.1:p.Phe1752del
NP_001092875.1:p.Phe1734del
NP_001153632.1:p.Phe1719del
NP_001153633.1:p.Phe1698del
NP_001341630.1:p.Phe1733del
NP_932173.1:p.Phe1752del
LRG_289t1:c.5254_5256del
LRG_289:g.103552TTC[1]
NC_000003.11:g.38592607_38592609del
NC_000003.11:g.38592609AGA[1]
NM_198056.2:c.5254_5256del

Protein change:

F1698del

Links:

dbSNP: rs2125826148

NCBI 1000 Genomes Browser:

rs2125826148

Molecular consequence:

NM_000335.5:c.5248TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001099404.2:c.5251TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001099405.2:c.5197TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001160160.2:c.5152TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001160161.2:c.5089TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354701.2:c.5194TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_198056.3:c.5251TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Functional consequence:

Absence of peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0083]

Condition(s)

Name:: Brugada syndrome 1 (BRGDA1)
Synonyms:: Right bundle branch block, ST segment elevation, and sudden death syndrome
Identifiers:: MONDO: MONDO:0011001; MedGen: C4551804; Orphanet: 130; OMIM: 601144

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Mus musculus proteolipid protein (myelin) 1 (Plp1), transcript variant 4, mRNA
Mus musculus proteolipid protein (myelin) 1 (Plp1), transcript variant 4, mRNA
gi|1315690801|ref|NM_001359117.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002588718	Roden Lab, Vanderbilt University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 1, 2022)	unknown, not applicable	clinical testing, research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002588718

Roden Lab, Vanderbilt University Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 1, 2022)

unknown, not applicable

clinical testing, research

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Roden Lab, Vanderbilt University Medical Center, SCV002588718.1

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

Description

The SCN5A variant c.5254_5256del (p.Phe1752del) NM_198056.2 was observed in an individual with Brugada Syndrome. Functional studies in HEK293T cells showed a complete absence of peak current, using a high-throughput method (PMID: 32533946). The variant is not observed in large population databases (PMID: 32461654). The variant is located in a hotspot region of the protein (transmembrane domain IV of pore-lining helix) (PMID: 32893267). Collectively, this evidence supports a classification of Likely Pathogenic.

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

Last Updated: Oct 13, 2024

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