NM_001035.3(RYR2):c.12568G>A (p.Val4190Met) AND Catecholaminergic polymorphic ventricular tachycardia 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 9, 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:: RCV002533701.10

Allele description [Variation Report for NM_001035.3(RYR2):c.12568G>A (p.Val4190Met)]

NM_001035.3(RYR2):c.12568G>A (p.Val4190Met)

Genes:

LOC126806068:BRD4-independent group 4 enhancer GRCh37_chr1:237947411-237948610 [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.12568G>A (p.Val4190Met)

HGVS:

NC_000001.11:g.237784280G>A
NG_008799.3:g.747097G>A
NM_001035.3:c.12568G>AMANE SELECT
NP_001026.2:p.Val4190Met
LRG_402t1:c.12568G>A
LRG_402:g.747097G>A
LRG_402p1:p.Val4190Met
NC_000001.10:g.237947580G>A
NG_008799.2:g.746879G>A
NM_001035.2:c.12568G>A

Protein change:

V4190M

Links:

dbSNP: rs1308975705

NCBI 1000 Genomes Browser:

rs1308975705

Molecular consequence:

NM_001035.3:c.12568G>A - 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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Homo sapiens 12 BAC RP11-469H8 (Roswell Park Cancer Institute Human BAC Library)...
Homo sapiens 12 BAC RP11-469H8 (Roswell Park Cancer Institute Human BAC Library) complete sequence
gi|22549680|gnl|bcmhgsc|project_haj lor|gb|AC025154.31|

Nucleotide
leukocyte immunoglobulin-like receptor, subfamily B, member 3 [Homo sapiens]
leukocyte immunoglobulin-like receptor, subfamily B, member 3 [Homo sapiens]
gi|5803060|ref|NP_006855.1|

Protein
5-formyltetrahydrofolate cyclo-ligase isoform X1 [Rattus norvegicus]
5-formyltetrahydrofolate cyclo-ligase isoform X1 [Rattus norvegicus]
gi|1958795436|ref|XP_038937095.1|

Protein
JGI_XZG46279.rev NIH_XGC_tropGas7 Xenopus tropicalis cDNA clone IMAGE:7561132 3'...
JGI_XZG46279.rev NIH_XGC_tropGas7 Xenopus tropicalis cDNA clone IMAGE:7561132 3', mRNA sequence
gi|57279944|gnl|dbEST|27085975|gb|C 13.1|

Nucleotide
Chain A, Ethanolamine utilization protein EutS
Chain A, Ethanolamine utilization protein EutS
gi|1877782554|pdb|6XPL|A

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000833041	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000833041

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 9, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV000833041.4

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 4190 of the RYR2 protein (p.Val4190Met). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR2 protein function. ClinVar contains an entry for this variant (Variation ID: 580536).

#	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: Oct 26, 2024

ClinVar

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