NM_000334.4(SCN4A):c.4379G>A (p.Arg1460Gln) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 19, 2023
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:: RCV000782203.2

Allele description [Variation Report for NM_000334.4(SCN4A):c.4379G>A (p.Arg1460Gln)]

NM_000334.4(SCN4A):c.4379G>A (p.Arg1460Gln)

Genes:

GH-LCR:growth hormone locus control region [Gene]
SCN4A:sodium voltage-gated channel alpha subunit 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.3

Genomic location:

Preferred name:

NM_000334.4(SCN4A):c.4379G>A (p.Arg1460Gln)

HGVS:

NC_000017.11:g.63941903C>T
NG_011699.1:g.36016G>A
NG_042788.1:g.24811C>T
NM_000334.4:c.4379G>AMANE SELECT
NP_000325.4:p.Arg1460Gln
NC_000017.10:g.62019263C>T

Protein change:

R1460Q

Links:

dbSNP: rs1210934866

NCBI 1000 Genomes Browser:

rs1210934866

Molecular consequence:

NM_000334.4:c.4379G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000920683	Gharavi Laboratory, Columbia University	no assertion criteria provided (ACMG Guidelines, 2015)	Uncertain significance (Sep 16, 2018)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV005201693	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 19, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000920683

Gharavi Laboratory, Columbia University

no assertion criteria provided

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 16, 2018)

germline

research

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

SCV005201693

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 19, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	yes	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 Gharavi Laboratory, Columbia University, SCV000920683.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV005201693.1

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

Description

Reported previously without a second variant in patients with muscle pain, muscle stiffness, myotonia, syncope, and non-sustained tachycardia (PMID: 21752396, 26036855); Published functional studies indicate that this variant alters channel dynamics, including voltage dependence and channel inactivation, resulting in a mix of loss of function and gain of function defects (PMID: 30824560); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34671263, 26036855, 30824560, 21752396)

#	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

Last Updated: Sep 29, 2024

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