NM_001035.3(RYR2):c.6320C>T (p.Thr2107Met) AND Catecholaminergic polymorphic ventricular tachycardia

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Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 24, 2019
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:: RCV000462358.4

Allele description

NM_001035.3(RYR2):c.6320C>T (p.Thr2107Met)

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.6320C>T (p.Thr2107Met)

HGVS:

NC_000001.11:g.237627960C>T
NG_008799.2:g.590559C>T
NG_008799.3:g.590777C>T
NM_001035.3:c.6320C>TMANE SELECT
NP_001026.2:p.Thr2107Met
LRG_402t1:c.6320C>T
LRG_402:g.590777C>T
LRG_402p1:p.Thr2107Met
NC_000001.10:g.237791260C>T
NM_001035.2:c.6320C>T

Protein change:

T2107M

Links:

dbSNP: rs370331492

NCBI 1000 Genomes Browser:

rs370331492

Molecular consequence:

NM_001035.3:c.6320C>T - missense variant - [Sequence Ontology: SO:0001583]

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

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Prevotella dentasini gene for 16S ribosomal RNA, partial sequence, strain: JCM 1...
Prevotella dentasini gene for 16S ribosomal RNA, partial sequence, strain: JCM 15908
gi|302129319|dbj|AB547681.1|

Nucleotide
Chain A, Probable copper-exporting P-type ATPase A
Chain A, Probable copper-exporting P-type ATPase A
gi|254574779|pdb|3A1E|A

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000541676	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 24, 2019)	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

SCV000541676

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 24, 2019)

germline

clinical testing

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

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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 Invitae, SCV000541676.4

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

Description

This sequence change replaces threonine with methionine at codon 2107 of the RYR2 protein (p.Thr2107Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs370331492, ExAC 0.01%). This variant has not been reported in the literature in individuals with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 178121). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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: Dec 24, 2022

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