NM_000335.5(SCN5A):c.3061C>T (p.Pro1021Ser) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 25, 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:: RCV002444735.9

Allele description [Variation Report for NM_000335.5(SCN5A):c.3061C>T (p.Pro1021Ser)]

NM_000335.5(SCN5A):c.3061C>T (p.Pro1021Ser)

Genes:

LOC110121269:VISTA enhancer hs2177 [Gene]
SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.3061C>T (p.Pro1021Ser)

Other names:

p.P1021S:CCC>TCC

HGVS:

NC_000003.12:g.38581098G>A
NG_008934.1:g.73575C>T
NG_053884.1:g.2837G>A
NM_000335.5:c.3061C>TMANE SELECT
NM_001099404.2:c.3061C>T
NM_001099405.2:c.3061C>T
NM_001160160.2:c.3061C>T
NM_001160161.2:c.3061C>T
NM_001354701.2:c.3061C>T
NM_198056.3:c.3061C>T
NP_000326.2:p.Pro1021Ser
NP_001092874.1:p.Pro1021Ser
NP_001092875.1:p.Pro1021Ser
NP_001153632.1:p.Pro1021Ser
NP_001153633.1:p.Pro1021Ser
NP_001341630.1:p.Pro1021Ser
NP_932173.1:p.Pro1021Ser
NP_932173.1:p.Pro1021Ser
LRG_289t1:c.3061C>T
LRG_289:g.73575C>T
LRG_289p1:p.Pro1021Ser
NC_000003.11:g.38622589G>A
NM_198056.2:c.3061C>T

Protein change:

P1021S

Links:

dbSNP: rs794728871

NCBI 1000 Genomes Browser:

rs794728871

Molecular consequence:

NM_000335.5:c.3061C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.3061C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.3061C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.3061C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.3061C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.3061C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.3061C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002753619	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23174487, 27566755, 30079003 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002753619

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 25, 2022)

germline

clinical testing

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

Citation Link

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

Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations.

Mullally J, Goldenberg I, Moss AJ, Lopes CM, Ackerman MJ, Zareba W, McNitt S, Robinson JL, Benhorin J, Kaufman ES, Towbin JA, Barsheshet A.

Heart Rhythm. 2013 Mar;10(3):378-82. doi: 10.1016/j.hrthm.2012.11.006. Epub 2012 Nov 19.

PubMed [citation]

PMID:: 23174487
PMCID:: PMC3690288

Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study.

Wilde AA, Moss AJ, Kaufman ES, Shimizu W, Peterson DR, Benhorin J, Lopes C, Towbin JA, Spazzolini C, Crotti L, Zareba W, Goldenberg I, Kanters JK, Robinson JL, Qi M, Hofman N, Tester DJ, Bezzina CR, Alders M, Aiba T, Kamakura S, Miyamoto Y, et al.

Circulation. 2016 Sep 20;134(12):872-82. doi: 10.1161/CIRCULATIONAHA.116.021823. Epub 2016 Aug 26.

PubMed [citation]

PMID:: 27566755
PMCID:: PMC5030177

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002753619.2

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

Description

The p.P1021S variant (also known as c.3061C>T), located in coding exon 16 of the SCN5A gene, results from a C to T substitution at nucleotide position 3061. The proline at codon 1021 is replaced by serine, an amino acid with similar properties. This alteration has been reported in long QT syndrome cohorts (Mullally J et al. Heart Rhythm, 2013 Mar;10:378-82; Wilde AA et al. Circulation, 2016 Sep;134:872-82). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Jun 2, 2024

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