NM_000540.3(RYR1):c.641C>T (p.Thr214Met) AND not provided

Germline classification:: Uncertain significance (6 submissions)
Last evaluated:: Jul 19, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000721610.29

Allele description [Variation Report for NM_000540.3(RYR1):c.641C>T (p.Thr214Met)]

NM_000540.3(RYR1):c.641C>T (p.Thr214Met)

Gene:

RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_000540.3(RYR1):c.641C>T (p.Thr214Met)

HGVS:

NC_000019.10:g.38446481C>T
NG_008866.1:g.17782C>T
NM_000540.3:c.641C>TMANE SELECT
NM_001042723.2:c.641C>T
NP_000531.2:p.Thr214Met
NP_000531.2:p.Thr214Met
NP_001036188.1:p.Thr214Met
LRG_766t1:c.641C>T
LRG_766:g.17782C>T
LRG_766p1:p.Thr214Met
NC_000019.9:g.38937121C>T
NM_000540.2(RYR1):c.641C>T
NM_000540.2:c.641C>T

Protein change:

T214M

Links:

dbSNP: rs727504129

NCBI 1000 Genomes Browser:

rs727504129

Molecular consequence:

NM_000540.3:c.641C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.641C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000203446	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Jan 13, 2014)	germline	clinical testing	Citation Link,
SCV000852707	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 28, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001799409	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001926569	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV003813147	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 7, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004021614	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jul 19, 2023)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Eurofins Ntd Llc (ga), SCV000203446.7

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

#	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		1	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000852707.1

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

#	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

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV001799409.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001926569.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003813147.2

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

#	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

From GeneDx, SCV004021614.1

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

Description

Observed in patients with malignant hyperthermia susceptibility, however, a second variant was also identified in some of these families that could explain this phenotype (Fiszer et al., 2015; Stephens et al., 2016; Miller et al., 2018; White et al., 2022); Observed with a second RYR1 variant in a patient with congenital myopathy, however, it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes, and the specific testing methodology was not described (Natera-de Benito et al., 2021); Published functional studies did not demonstrate a damaging effect (Stephens et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30236257, 25658027, 33767344, 36208971, 32381029, 33333461, 27857962)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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