NM_001232.4(CASQ2):c.748C>T (p.Arg250Cys) AND Catecholaminergic polymorphic ventricular tachycardia 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 6, 2022
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:: RCV002532267.9

Allele description [Variation Report for NM_001232.4(CASQ2):c.748C>T (p.Arg250Cys)]

NM_001232.4(CASQ2):c.748C>T (p.Arg250Cys)

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.748C>T (p.Arg250Cys)

HGVS:

NC_000001.11:g.115725543G>A
NG_008802.1:g.48263C>T
NM_001232.4:c.748C>TMANE SELECT
NP_001223.2:p.Arg250Cys
NP_001223.2:p.Arg250Cys
LRG_404t1:c.748C>T
LRG_404:g.48263C>T
LRG_404p1:p.Arg250Cys
NC_000001.10:g.116268164G>A
NM_001232.3:c.748C>T

Protein change:

R250C

Links:

dbSNP: rs151115064

NCBI 1000 Genomes Browser:

rs151115064

Molecular consequence:

NM_001232.4:c.748C>T - missense variant - [Sequence Ontology: SO:0001583]

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

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Canis lupus familiaris endothelin 3 (EDN3), mRNA
Canis lupus familiaris endothelin 3 (EDN3), mRNA
gi|50950152|ref|NM_001002942.1|

Nucleotide
PREDICTED: Canis lupus familiaris glycoprotein nmb (GPNMB), transcript variant X...
PREDICTED: Canis lupus familiaris glycoprotein nmb (GPNMB), transcript variant X5, mRNA
gi|1952684944|ref|XM_539472.7|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000822928	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 6, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30600839, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000822928

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 6, 2022)

germline

clinical testing

PubMed (2)
[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

A novel variant of the CASQ2 gene in a Chinese family with catecholaminergic polymorphic ventricular tachycardia.

Gao L, Cui L, Zheng L, Zhao Z, Li Q, Yu X, Wang J, Yuan Y.

Cardiol J. 2018;25(6):756-758. doi: 10.5603/CJ.2018.0155. No abstract available.

PubMed [citation]

PMID:: 30600839

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000822928.4

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

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 250 of the CASQ2 protein (p.Arg250Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with catecholaminergic polymorphic ventricular tachycardia (PMID: 30600839). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 572954). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Nov 3, 2024

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