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NM_174934.4(SCN4B):c.61+1G>A AND Long QT syndrome 10

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 16, 2021
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:
RCV000853595.7

Allele description [Variation Report for NM_174934.4(SCN4B):c.61+1G>A]

NM_174934.4(SCN4B):c.61+1G>A

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.61+1G>A
HGVS:
  • NC_000011.10:g.118152612C>T
  • NG_011710.1:g.5304G>A
  • NM_001142348.2:c.61+1G>A
  • NM_174934.4:c.61+1G>AMANE SELECT
  • LRG_330t1:c.61+1G>A
  • LRG_330:g.5304G>A
  • NC_000011.9:g.118023327C>T
  • NC_000011.9:g.118023327C>T
  • NM_174934.3:c.61+1G>A
Links:
dbSNP: rs377558816
NCBI 1000 Genomes Browser:
rs377558816
Molecular consequence:
  • NM_001142348.2:c.61+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_174934.4:c.61+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000996563Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 17, 2019) 		unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002157639Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 16, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933
See all PubMed Citations (3)

Details of each submission

From Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues, SCV000996563.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV002157639.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with SCN4B-related conditions. ClinVar contains an entry for this variant (Variation ID: 692252). This variant is present in population databases (rs377558816, ExAC 0.003%). This sequence change affects a donor splice site in intron 1 of the SCN4B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SCN4B cause disease.

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

Last Updated: Feb 28, 2024