NM_001232.4(CASQ2):c.546del (p.Phe182fs) AND Catecholaminergic polymorphic ventricular tachycardia 1

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

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 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:: RCV000208054.11

Allele description

NM_001232.4(CASQ2):c.546del (p.Phe182fs)

Gene:

CASQ2:calsequestrin 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p13.1

Genomic location:

Preferred name:

NM_001232.4(CASQ2):c.546del (p.Phe182fs)

HGVS:

NC_000001.11:g.115732964del
NG_008802.1:g.40845del
NM_001232.4:c.546delMANE SELECT
NP_001223.2:p.Phe182fs
LRG_404t1:c.546del
LRG_404:g.40845del
NC_000001.10:g.116275582del
NC_000001.10:g.116275585del
NM_001232.3:c.546delT

Protein change:

F182fs

Links:

dbSNP: rs763955301

NCBI 1000 Genomes Browser:

rs763955301

Molecular consequence:

NM_001232.4:c.546del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV000263805	Blueprint Genetics	criteria provided, single submitter (Variant Classification)	Likely pathogenic (Jan 26, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19398665, 21618644 Citation Link,
SCV002198977	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 28, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 12386154, 19398665, 21618644, 29544605, 32693635, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000263805

Blueprint Genetics

criteria provided, single submitter

(Variant Classification)

Likely pathogenic
(Jan 26, 2015)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002198977

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 28, 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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Absence of calsequestrin 2 causes severe forms of catecholaminergic polymorphic ventricular tachycardia.

Postma AV, Denjoy I, Hoorntje TM, Lupoglazoff JM, Da Costa A, Sebillon P, Mannens MM, Wilde AA, Guicheney P.

Circ Res. 2002 Oct 18;91(8):e21-6.

PubMed [citation]

PMID:: 12386154

Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia.

Hayashi M, Denjoy I, Extramiana F, Maltret A, Buisson NR, Lupoglazoff JM, Klug D, Hayashi M, Takatsuki S, Villain E, Kamblock J, Messali A, Guicheney P, Lunardi J, Leenhardt A.

Circulation. 2009 May 12;119(18):2426-34. doi: 10.1161/CIRCULATIONAHA.108.829267. Epub 2009 Apr 27.

PubMed [citation]

PMID:: 19398665

See all PubMed Citations (6)

Details of each submission

From Blueprint Genetics, SCV000263805.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

#	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 Invitae, SCV002198977.3

#	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 creates a premature translational stop signal (p.Phe182Leufs*28) in the CASQ2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CASQ2 are known to be pathogenic (PMID: 12386154). This variant is present in population databases (rs763955301, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with clinical features of catecholaminergic polymorphic ventricular tachycardia (PMID: 19398665, 21618644, 29544605, 32693635). ClinVar contains an entry for this variant (Variation ID: 222522). 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 16, 2024

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