NM_000334.4(SCN4A):c.3478A>G (p.Ile1160Val) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 10, 2017
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:: RCV000497702.2

Allele description [Variation Report for NM_000334.4(SCN4A):c.3478A>G (p.Ile1160Val)]

NM_000334.4(SCN4A):c.3478A>G (p.Ile1160Val)

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.3478A>G (p.Ile1160Val)

HGVS:

NC_000017.11:g.63945602T>C
NG_011699.1:g.32317A>G
NG_042788.1:g.28510T>C
NM_000334.4:c.3478A>GMANE SELECT
NP_000325.4:p.Ile1160Val
NC_000017.10:g.62022962T>C
P35499:p.Ile1160Val

Protein change:

I1160V; ILE1160VAL

Links:

UniProtKB: P35499#VAR_017793; OMIM: 603967.0010; dbSNP: rs121908549

NCBI 1000 Genomes Browser:

rs121908549

Molecular consequence:

NM_000334.4:c.3478A>G - 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
SCV000589563	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (May 10, 2017)	germline	clinical testing	Citation Link,
SCV000615087	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Feb 13, 2017)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 18337730, 15037716, 22759684, 23884711, 3822145, 8058156, 9336185, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000589563

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(May 10, 2017)

germline

clinical testing

Citation Link,

SCV000615087

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Feb 13, 2017)

germline

clinical testing

PubMed (8)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

In tandem analysis of CLCN1 and SCN4A greatly enhances mutation detection in families with non-dystrophic myotonia.

Trip J, Drost G, Verbove DJ, van der Kooi AJ, Kuks JB, Notermans NC, Verschuuren JJ, de Visser M, van Engelen BG, Faber CG, Ginjaar IB.

Eur J Hum Genet. 2008 Aug;16(8):921-9. doi: 10.1038/ejhg.2008.39. Epub 2008 Mar 12.

PubMed [citation]

PMID:: 18337730

Periodic paralysis mutation MiRP2-R83H in controls: Interpretations and general recommendation.

Jurkat-Rott K, Lehmann-Horn F.

Neurology. 2004 Mar 23;62(6):1012-5.

PubMed [citation]

PMID:: 15037716

See all PubMed Citations (8)

Details of each submission

From GeneDx, SCV000589563.3

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

Description

The I1160V variant in the SCN4A gene has been reported previously in the heterozygous state in mutiple unrelatedindividuals with acetazolamide-responsive myotonia congenita or paramyotonia congenita(Jurkatt-Rott et al., 2004; Al-Ghamdi et al., 2017). Functional studies demonstrate that the I1160Vvariant has faster rates of closed-state fast inactivation onset and recovery as well as slowerdeactivation as compared to wild-type (Richmond et al., 1997). The I1160V variant is not observed inlarge population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome VariantServer). The I1160V variant is a conservative amino acid substitution that occurs at a position that isconserved across species. We interpret I1160V as a pathogenic variant.

#	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 Athena Diagnostics, SCV000615087.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

#	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 29, 2024

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