NM_174934.4(SCN4B):c.239T>C (p.Ile80Thr) AND Long QT syndrome 10

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 21, 2016
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:: RCV000227966.6

Allele description [Variation Report for NM_174934.4(SCN4B):c.239T>C (p.Ile80Thr)]

NM_174934.4(SCN4B):c.239T>C (p.Ile80Thr)

Genes:

LOC126861356:BRD4-independent group 4 enhancer GRCh37_chr11:118014519-118015718 [Gene]
SCN4B:sodium voltage-gated channel beta subunit 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_174934.4(SCN4B):c.239T>C (p.Ile80Thr)

HGVS:

NC_000011.10:g.118144057A>G
NG_011710.1:g.13859T>C
NM_001142348.2:c.62-2721T>C
NM_001142349.2:c.-92T>C
NM_174934.4:c.239T>CMANE SELECT
NP_777594.1:p.Ile80Thr
NP_777594.1:p.Ile80Thr
LRG_330t1:c.239T>C
LRG_330:g.13859T>C
LRG_330p1:p.Ile80Thr
NC_000011.9:g.118014772A>G
NM_174934.3:c.239T>C
NR_024527.2:n.382T>C

Protein change:

I80T

Links:

dbSNP: rs546190140

NCBI 1000 Genomes Browser:

rs546190140

Molecular consequence:

NM_001142349.2:c.-92T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001142348.2:c.62-2721T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_174934.4:c.239T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_024527.2:n.382T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Long QT syndrome 10 (LQT10)
Identifiers:: MONDO: MONDO:0012737; MedGen: C2678484; Orphanet: 101016; Orphanet: 768; OMIM: 611819

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000291590	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 21, 2016)	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

SCV000291590

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 21, 2016)

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

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000291590.5

#	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 replaces isoleucine with threonine at codon 80 of the SCN4B protein (p.Ile80Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs546190140, ExAC 0.01%) but has not been reported in the literature in individuals with a SCN4B-related disease.

#	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: Feb 28, 2024

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