NM_001035.3(RYR2):c.814C>T (p.Arg272Cys) AND Catecholaminergic polymorphic ventricular tachycardia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 30, 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:: RCV004001737.2

Allele description [Variation Report for NM_001035.3(RYR2):c.814C>T (p.Arg272Cys)]

NM_001035.3(RYR2):c.814C>T (p.Arg272Cys)

Gene:

RYR2:ryanodine receptor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_001035.3(RYR2):c.814C>T (p.Arg272Cys)

HGVS:

NC_000001.11:g.237417089C>T
NG_008799.3:g.379906C>T
NM_001035.3:c.814C>TMANE SELECT
NP_001026.2:p.Arg272Cys
LRG_402t1:c.814C>T
LRG_402:g.379906C>T
LRG_402p1:p.Arg272Cys
NC_000001.10:g.237580389C>T
NG_008799.2:g.379688C>T
NM_001035.2:c.814C>T

Protein change:

R272C

Links:

dbSNP: rs771847292

NCBI 1000 Genomes Browser:

rs771847292

Molecular consequence:

NM_001035.3:c.814C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Catecholaminergic polymorphic ventricular tachycardia (CVPT)
Synonyms:: Familial polymorphic ventricular tachycardia; Catecholamine-induced polymorphic ventricular tachycardia; Polymorphic catecholergic ventricular tachycardia
Identifiers:: MONDO: MONDO:0017990; MedGen: C5574922; Orphanet: 3286; OMIM: PS604772

Recent activity

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Procollagen lysine, 2-oxoglutarate 5-dioxygenase 2 [Mus musculus]
Procollagen lysine, 2-oxoglutarate 5-dioxygenase 2 [Mus musculus]
gi|18204027|gb|AAH21352.1|

Protein
Chain C, DNA REPLICATION FACTOR CDT1
Chain C, DNA REPLICATION FACTOR CDT1
gi|262118476|pdb|2WVR|C

Protein
Besleria hirsuta AND 1[s_discriminator] (0)
dbGaP
Besleria hirsuta (0)
GEO DataSets
DKFZp434P0914_r1 434 (synonym: htes3) Homo sapiens cDNA clone DKFZp434P0914 5', ...
DKFZp434P0914_r1 434 (synonym: htes3) Homo sapiens cDNA clone DKFZp434P0914 5', mRNA sequence
gi|5409650|gnl|dbEST|2888844|emb|AL 4.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004827092	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Oct 30, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33325730, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004827092

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Oct 30, 2023)

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	3	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Genetic Association Between Hypoplastic Left Heart Syndrome and Cardiomyopathies.

Theis JL, Hu JJ, Sundsbak RS, Evans JM, Bamlet WR, Qureshi MY, O'Leary PW, Olson TM.

Circ Genom Precis Med. 2021 Feb;14(1):e003126. doi: 10.1161/CIRCGEN.120.003126. Epub 2020 Dec 16.

PubMed [citation]

PMID:: 33325730

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004827092.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces arginine with cysteine at codon 272 of the RYR2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a proband affected with hypoplastic left heart syndrome, as well as in another four family members including two with confirmed heart diseases and two with normal echocardiograms (PMID: 33325730). This variant has been identified in 1/249146 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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	108544	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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