NM_000335.5(SCN5A):c.5899A>G (p.Ile1967Val) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 7, 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:: RCV003994615.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.5899A>G (p.Ile1967Val)]

NM_000335.5(SCN5A):c.5899A>G (p.Ile1967Val)

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.5899A>G (p.Ile1967Val)

HGVS:

NC_000003.12:g.38550470T>C
NG_008934.1:g.104203A>G
NM_000335.5:c.5899A>GMANE SELECT
NM_001099404.2:c.5902A>G
NM_001099405.2:c.5848A>G
NM_001160160.2:c.5803A>G
NM_001160161.2:c.5740A>G
NM_001354701.2:c.5845A>G
NM_198056.3:c.5902A>G
NP_000326.2:p.Ile1967Val
NP_000326.2:p.Ile1967Val
NP_001092874.1:p.Ile1968Val
NP_001092874.1:p.Ile1968Val
NP_001092875.1:p.Ile1950Val
NP_001153632.1:p.Ile1935Val
NP_001153633.1:p.Ile1914Val
NP_001341630.1:p.Ile1949Val
NP_932173.1:p.Ile1968Val
NP_932173.1:p.Ile1968Val
LRG_289t1:c.5902A>G
LRG_289t2:c.5899A>G
LRG_289t3:c.5902A>G
LRG_289:g.104203A>G
LRG_289p1:p.Ile1968Val
LRG_289p2:p.Ile1967Val
LRG_289p3:p.Ile1968Val
NC_000003.11:g.38591961T>C
NM_000335.4:c.5899A>G
NM_001099404.1:c.5902A>G
NM_198056.2:c.5902A>G
NR_176299.1:n.6648A>G

Protein change:

I1914V

Molecular consequence:

NM_000335.5:c.5899A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.5902A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.5848A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.5803A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.5740A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.5845A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.5902A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_176299.1:n.6648A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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protein phosphatase 1 regulatory subunit 3B [Rattus norvegicus]
protein phosphatase 1 regulatory subunit 3B [Rattus norvegicus]
gi|48675870|ref|NP_620267.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004812272	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 7, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004812272

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 7, 2024)

germline

clinical testing

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	germline	unknown	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 Molecular Genetics, Royal Melbourne Hospital, SCV004812272.1

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

Description

This sequence change in SCN5A is predicted to replace isoleucine with valine at codon 1967, p.(Ile1967Val). The isoleucine residue is moderately conserved (100 vertebrates, Multiz Alignments), and is located in a cytoplasmic region. This variant is absent from the population database gnomAD v2.1 and v3.1. To our knowledge, this variant has not been previously reported in the relevant scientific literature or databases. Computational evidence predicts a benign effect for the missense substitution (REVEL = 0.284). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, BP4.

#	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: May 7, 2024

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