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NM_000335.5(SCN5A):c.3214_3215inv (p.Glu1072Ser) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 2, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001841489.14

Allele description [Variation Report for NM_000335.5(SCN5A):c.3214_3215inv (p.Glu1072Ser)]

NM_000335.5(SCN5A):c.3214_3215inv (p.Glu1072Ser)

Genes:
LOC110121269:VISTA enhancer hs2177 [Gene]
SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]
Variant type:
Inversion
Cytogenetic location:
3p22.2
Genomic location:
Preferred name:
NM_000335.5(SCN5A):c.3214_3215inv (p.Glu1072Ser)
HGVS:
  • NC_000003.12:g.38580944_38580945inv
  • NG_008934.1:g.73728_73729inv
  • NG_053884.1:g.2683_2684inv
  • NM_000335.5:c.3214_3215invMANE SELECT
  • NM_001099404.2:c.3214_3215inv
  • NM_001099405.2:c.3214_3215inv
  • NM_001160160.2:c.3214_3215inv
  • NM_001160161.2:c.3214_3215inv
  • NM_001354701.2:c.3214_3215inv
  • NM_198056.3:c.3214_3215inv
  • NP_000326.2:p.Glu1072Ser
  • NP_001092874.1:p.Glu1072Ser
  • NP_001092875.1:p.Glu1072Ser
  • NP_001153632.1:p.Glu1072Ser
  • NP_001153633.1:p.Glu1072Ser
  • NP_001341630.1:p.Glu1072Ser
  • NP_932173.1:p.Glu1072Ser
  • NP_932173.1:p.Glu1072Ser
  • LRG_289t1:c.3214_3215inv
  • LRG_289:g.73728_73729inv
  • LRG_289p1:p.Glu1072Ser
  • NC_000003.11:g.38622435_38622436delinsGA
  • NC_000003.11:g.38622435_38622436inv
  • NM_198056.2:c.3214_3215delGAinsTC
  • NM_198056.2:c.3214_3215delinsTC
  • NM_198056.2:c.3214_3215inv
  • NM_198056.3:c.3214_3215delinsTC
Protein change:
E1072S
Links:
Molecular consequence:
  • NM_000335.5:c.3214_3215inv - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.3214_3215inv - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.3214_3215inv - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.3214_3215inv - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.3214_3215inv - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.3214_3215inv - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.3214_3215inv - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Cardiac arrhythmia
Synonyms:
Cardiac rhythm disease
Identifiers:
EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001343146Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jun 26, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004833372All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Oct 2, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot provided108544not providedclinical testing

Citations

PubMed

Brugada syndrome genetics is associated with phenotype severity.

Ciconte G, Monasky MM, Santinelli V, Micaglio E, Vicedomini G, Anastasia L, Negro G, Borrelli V, Giannelli L, Santini F, de Innocentiis C, Rondine R, Locati ET, Bernardini A, Mazza BC, Mecarocci V, Ćalović Ž, Ghiroldi A, D'Imperio S, Benedetti S, Di Resta C, Rivolta I, et al.

Eur Heart J. 2021 Mar 14;42(11):1082-1090. doi: 10.1093/eurheartj/ehaa942.

PubMed [citation]
PMID:
33221895
PMCID:
PMC7955973

Clinical characteristics and electrophysiologic properties of SCN5A variants in fever-induced Brugada syndrome.

Chen GX, Barajas-Martínez H, Ciconte G, Wu CI, Monasky MM, Xia H, Li B, Capra JA, Guo K, Zhang ZH, Chen X, Yang B, Jiang H, Tse G, Mak CM, Aizawa Y, Gollob MH, Antzelevitch C, Wilde AAM, Pappone C, Hu D.

EBioMedicine. 2023 Jan;87:104388. doi: 10.1016/j.ebiom.2022.104388. Epub 2022 Dec 12.

PubMed [citation]
PMID:
36516610
PMCID:
PMC9768239
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001343146.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This missense variant (also known as c.3214_3215delinsTC in published literature due to the use of alternate nomenclature) replaces glutamic acid with serine at codon 1072 of the SCN5A protein. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individual(s) affected with Brugada syndrome (PMID: 33221895, 36516610). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004833372.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (3)

Description

This missense variant (also known as c.3214_3215delinsTC in published literature due to the use of alternate nomenclature) replaces glutamic acid with serine at codon 1072 of the SCN5A protein. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individual(s) affected with Brugada syndrome (PMID: 33221895, 36516610). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided2not providednot providednot provided

Last Updated: May 3, 2025