NM_000069.3(CACNA1S):c.3716G>A (p.Arg1239His) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Mar 28, 2023
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:: RCV000414086.18

Allele description

NM_000069.3(CACNA1S):c.3716G>A (p.Arg1239His)

Gene:

CACNA1S:calcium voltage-gated channel subunit alpha1 S [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q32.1

Genomic location:

Preferred name:

NM_000069.3(CACNA1S):c.3716G>A (p.Arg1239His)

Other names:

NM_000069.2(CACNA1S):c.3716G>A(p.Arg1239His)

HGVS:

NC_000001.11:g.201053538C>T
NG_009816.2:g.64029G>A
NM_000069.3:c.3716G>AMANE SELECT
NP_000060.2:p.Arg1239His
NC_000001.10:g.201022666C>T
NG_009816.1:g.64029G>A
NM_000069.2:c.3716G>A
Q13698:p.Arg1239His

Protein change:

R1239H; ARG1239HIS

Links:

UniProtKB: Q13698#VAR_001502; OMIM: 114208.0001; dbSNP: rs28930068

NCBI 1000 Genomes Browser:

rs28930068

Molecular consequence:

NM_000069.3:c.3716G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000342944	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Jun 17, 2016)	germline	clinical testing	Citation Link,
SCV000490450	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 3, 2022)	germline	clinical testing	Citation Link,
SCV002562964	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Oct 1, 2021)	germline	clinical testing	Citation Link,
SCV004229525	Athena Diagnostics Inc	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Mar 28, 2023)	unknown	clinical testing	PubMed (18) [See all records that cite these PMIDs] 34608571, 11591859, 28857175, 19225109, 30090141, 11555352, 31068157, 34008892, 33184660, 33042247, 35509735, 34804722, 8004673, 18162704, 17418573, 19118277, 7847370, 26467025

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes.

Brugnoni R, Canioni E, Filosto M, Pini A, Tonin P, Rossi T, Canavese C, Eoli M, Siciliano G, Lauria G, Mantegazza R, Maggi L.

Neurogenetics. 2022 Jan;23(1):19-25. doi: 10.1007/s10048-021-00673-2. Epub 2021 Oct 5.

PubMed [citation]

PMID:: 34608571

Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK.

Davies NP, Eunson LH, Samuel M, Hanna MG.

Neurology. 2001 Oct 9;57(7):1323-5.

PubMed [citation]

PMID:: 11591859

See all PubMed Citations (18)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000342944.4

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

#	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		1	not provided	not provided	not provided

From GeneDx, SCV000490450.4

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

Description

Published functional studies demonstrate membrane depolarization (Jurkat-Rott et al., 2009); Not observed in large population cohorts (Lek et al., 2016); 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: 10639629, 7847370, 16767662, 30090141, 11555352, 17418573, 19225109, 28857175, 31068157, 31567646, 33184660, 29572832, 11591859, 33042247, 9066893, 7650604, 19118277)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV002562964.9

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

#	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		1	not provided	not provided	not provided

From Athena Diagnostics Inc, SCV004229525.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (18)

Description

This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with HOKPP and segregates with disease in multiple families. At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic. Computational tools predict that this variant is damaging.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 10, 2024

ClinVar

Relating variation to medicine