NM_001232.4(CASQ2):c.974_983del (p.Asp325fs) AND Catecholaminergic polymorphic ventricular tachycardia 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 26, 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:: RCV003844652.2

Allele description [Variation Report for NM_001232.4(CASQ2):c.974_983del (p.Asp325fs)]

NM_001232.4(CASQ2):c.974_983del (p.Asp325fs)

Gene:

CASQ2:calsequestrin 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p13.1

Genomic location:

Preferred name:

NM_001232.4(CASQ2):c.974_983del (p.Asp325fs)

HGVS:

NC_000001.11:g.115702953_115702962del
NG_008802.1:g.70845_70854del
NM_001232.4:c.974_983delMANE SELECT
NP_001223.2:p.Asp325Glyfs
NP_001223.2:p.Asp325fs
LRG_404t1:c.973_982del
LRG_404:g.70845_70854del
LRG_404p1:p.Asp325Glyfs
NC_000001.10:g.116245573_116245582del
NC_000001.10:g.116245574_116245583del
NM_001232.3:c.973_982delGACCTATTCA

Protein change:

D325fs

Molecular consequence:

NM_001232.4:c.974_983del - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004648914	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 26, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23595086, 30729048, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004648914

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 26, 2023)

germline

clinical testing

PubMed (3)
[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

Genetic background of catecholaminergic polymorphic ventricular tachycardia in Japan.

Kawamura M, Ohno S, Naiki N, Nagaoka I, Dochi K, Wang Q, Hasegawa K, Kimura H, Miyamoto A, Mizusawa Y, Itoh H, Makiyama T, Sumitomo N, Ushinohama H, Oyama K, Murakoshi N, Aonuma K, Horigome H, Honda T, Yoshinaga M, Ito M, Horie M.

Circ J. 2013;77(7):1705-13. Epub 2013 Apr 18. Erratum in: Circ J. 2020;84(11):2124-2126. doi: 10.1253/circj.CJ-66-0186.

PubMed [citation]

PMID:: 23595086

A Homozygous CASQ2 Mutation in a Japanese Patient with Catecholaminergic Polymorphic Ventricular Tachycardia.

Fujisawa T, Aizawa Y, Katsumata Y, Udo A, Ito S, Hatakeyama K, Hirose M, Miyama H, Nakajima K, Nishiyama T, Kimura T, Nitta M, Misumi K, Takatsuki S, Kosaki K, Fukuda K.

Case Rep Genet. 2019;2019:9056596. doi: 10.1155/2019/9056596.

PubMed [citation]

PMID:: 30729048
PMCID:: PMC6341267

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004648914.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Asp325Glyfs*7) in the CASQ2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 75 amino acid(s) of the CASQ2 protein. This variant is present in population databases (no rsID available, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with CASQ2-related conditions. This variant disrupts a region of the CASQ2 protein in which other variant(s) (p.W361*) 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: Sep 29, 2024

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