NM_001035.3(RYR2):c.950T>C (p.Met317Thr) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 10, 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:: RCV001188885.12

Allele description [Variation Report for NM_001035.3(RYR2):c.950T>C (p.Met317Thr)]

NM_001035.3(RYR2):c.950T>C (p.Met317Thr)

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.950T>C (p.Met317Thr)

Other names:

p.Met317Thr

HGVS:

NC_000001.11:g.237423193T>C
NG_008799.3:g.386010T>C
NM_001035.3:c.950T>CMANE SELECT
NP_001026.2:p.Met317Thr
LRG_402t1:c.950T>C
LRG_402:g.386010T>C
LRG_402p1:p.Met317Thr
NC_000001.10:g.237586493T>C
NG_008799.2:g.385792T>C
NM_001035.2:c.950T>C

Protein change:

M317T

Links:

dbSNP: rs367601258

NCBI 1000 Genomes Browser:

rs367601258

Molecular consequence:

NM_001035.3:c.950T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001356057	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29544605, 30847666, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001356057

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 10, 2023)

germline

clinical testing

PubMed (3)
[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

Cardiac Genetic Predisposition in Sudden Infant Death Syndrome.

Tester DJ, Wong LCH, Chanana P, Jaye A, Evans JM, FitzPatrick DR, Evans MJ, Fleming P, Jeffrey I, Cohen MC, Tfelt-Hansen J, Simpson MA, Behr ER, Ackerman MJ.

J Am Coll Cardiol. 2018 Mar 20;71(11):1217-1227. doi: 10.1016/j.jacc.2018.01.030.

PubMed [citation]

PMID:: 29544605

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]

PMID:: 30847666
PMCID:: PMC6533346

See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001356057.3

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

Description

This missense variant replaces methionine with threonine at codon 317 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden infant death syndrome (PMID: 29544605) and in another individual affected with unspecified arrhythmia (PMID: 30847666). This variant has been identified in 9/280154 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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