NM_000335.5(SCN5A):c.1190T>C (p.Ile397Thr) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 6, 2024
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:: RCV000498420.4

Allele description

NM_000335.5(SCN5A):c.1190T>C (p.Ile397Thr)

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.1190T>C (p.Ile397Thr)

HGVS:

NC_000003.12:g.38606099A>G
NG_008934.1:g.48574T>C
NM_000335.5:c.1190T>CMANE SELECT
NM_001099404.2:c.1190T>C
NM_001099405.2:c.1190T>C
NM_001160160.2:c.1190T>C
NM_001160161.2:c.1190T>C
NM_001354701.2:c.1190T>C
NM_198056.3:c.1190T>C
NP_000326.2:p.Ile397Thr
NP_001092874.1:p.Ile397Thr
NP_001092875.1:p.Ile397Thr
NP_001153632.1:p.Ile397Thr
NP_001153633.1:p.Ile397Thr
NP_001341630.1:p.Ile397Thr
NP_932173.1:p.Ile397Thr
NP_932173.1:p.Ile397Thr
LRG_289t1:c.1190T>C
LRG_289:g.48574T>C
LRG_289p1:p.Ile397Thr
NC_000003.11:g.38647590A>G
NM_198056.2:c.1190T>C
Q14524:p.Ile397Thr

Protein change:

I397T

Links:

UniProtKB: Q14524#VAR_074706; dbSNP: rs199473105

NCBI 1000 Genomes Browser:

rs199473105

Molecular consequence:

NM_000335.5:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.1190T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

CPT1A carnitine palmitoyltransferase 1A [Homo sapiens]
CPT1A carnitine palmitoyltransferase 1A [Homo sapiens]
Gene ID:1374

Gene
Gene Links for GEO Profiles (Select 116322771) (1)
Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000589536	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Mar 17, 2021)	germline	clinical testing	Citation Link,
SCV001227990	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 6, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19716085, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000589536

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Mar 17, 2021)

germline

clinical testing

Citation Link,

SCV001227990

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 6, 2024)

germline

clinical testing

PubMed (2)
[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

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]

PMID:: 19716085
PMCID:: PMC3049907

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV000589536.5

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

Description

Observed in an individual referred for LQTS genetic testing (Kapplinger et al., 2009); Not observed in large population cohorts (Lek et al., 2016); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID #67644; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 19716085)

#	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 Invitae, SCV001227990.4

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 397 of the SCN5A protein (p.Ile397Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with referral for long QT syndrome testing (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67644). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 8, 2024

ClinVar

Relating variation to medicine