NM_001232.4(CASQ2):c.1014+1G>A AND Catecholaminergic polymorphic ventricular tachycardia 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 13, 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:: RCV002564387.9

Allele description [Variation Report for NM_001232.4(CASQ2):c.1014+1G>A]

NM_001232.4(CASQ2):c.1014+1G>A

Gene:

CASQ2:calsequestrin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p13.1

Genomic location:

Preferred name:

NM_001232.4(CASQ2):c.1014+1G>A

HGVS:

NC_000001.11:g.115702920C>T
NG_008802.1:g.70886G>A
NM_001232.4:c.1014+1G>AMANE SELECT
LRG_404:g.70886G>A
NC_000001.10:g.116245541C>T

Links:

dbSNP: rs1654250819

NCBI 1000 Genomes Browser:

rs1654250819

Molecular consequence:

NM_001232.4:c.1014+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Catecholaminergic polymorphic ventricular tachycardia 1
Synonyms:: VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 1, WITH OR WITHOUT ATRIAL DYSFUNCTION AND/OR DILATED CARDIOMYOPATHY; Stress-induced polymorphic ventricular tachycardia; VENTRICULAR TACHYCARDIA, STRESS-INDUCED POLYMORPHIC 1
Identifiers:: MONDO: MONDO:0011484; MedGen: C1631597; Orphanet: 3286; OMIM: 604772

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
SCV002247437	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 13, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 21618644, 17576681, 9536098, 23595086, 30729048, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002247437

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 13, 2023)

germline

clinical testing

PubMed (6)
[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

Citations

PubMed

Functional analysis reveals splicing mutations of the CASQ2 gene in patients with CPVT: implication for genetic counselling and clinical management.

Roux-Buisson N, Rendu J, Denjoy I, Guicheney P, Goldenberg A, David N, Faivre L, Barthez O, Danieli GA, Marty I, Lunardi J, Fauré J.

Hum Mutat. 2011 Sep;32(9):995-9. doi: 10.1002/humu.21537. Epub 2011 Aug 5.

PubMed [citation]

PMID:: 21618644

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV002247437.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change affects a donor splice site in intron 10 of the CASQ2 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with autosomal recessive catecholaminergic polymorphic ventricular tachycardia (PMID: 21618644). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1457736). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the CASQ2 protein in which other variant(s) (p.Trp361*) have been determined to be pathogenic (PMID: 23595086, 30729048). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: May 1, 2024

ClinVar

Relating variation to medicine