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NM_000540.2(RYR1):c.7923C>G (p.Leu2641=)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(1);Likely benign(8);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
10 (Most recent: Jul 4, 2021)
Last evaluated:
Jun 1, 2021
Accession:
VCV000197609.11
Variation ID:
197609
Description:
single nucleotide variant
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NM_000540.2(RYR1):c.7923C>G (p.Leu2641=)

Allele ID
194770
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19q13.2
Genomic location
19: 38502967 (GRCh38) GRCh38 UCSC
19: 38993607 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.10:g.38502967C>G
NC_000019.9:g.38993607C>G
NM_000540.2:c.7923C>G NP_000531.2:p.Leu2641= synonymous
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000019.10:38502966:C:G
Functional consequence
-
Global minor allele frequency (GMAF)
0.00060 (G)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00271
1000 Genomes Project 0.00060
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00108
Exome Aggregation Consortium (ExAC) 0.00116
The Genome Aggregation Database (gnomAD), exomes 0.00109
Trans-Omics for Precision Medicine (TOPMed) 0.00092
Links
ClinGen: CA024874
dbSNP: rs142558977
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 2 criteria provided, multiple submitters, no conflicts Mar 8, 2018 RCV000245786.6
Likely benign 1 criteria provided, single submitter May 3, 2018 RCV000282044.2
Likely benign 1 criteria provided, single submitter May 3, 2018 RCV000335516.2
Likely benign 1 criteria provided, single submitter May 3, 2018 RCV000337138.2
Likely benign 1 criteria provided, single submitter Jun 14, 2016 RCV000408287.1
Benign 1 criteria provided, single submitter Nov 30, 2020 RCV001085362.2
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Jun 1, 2021 RCV000721683.8
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
RYR1 No evidence available No evidence available GRCh38
GRCh37
3931 3945

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(-)
criteria provided, single submitter
Method: clinical testing
NOT SPECIFIED
Allele origin: germline
PreventionGenetics,PreventionGenetics
Accession: SCV000305030.1
Submitted: (Apr 28, 2016)
Evidence details
Likely benign
(Jun 14, 2016)
criteria provided, single submitter
Method: clinical testing
Congenital Neuromuscular Disease with Uniform Type 1 Fiber
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000412520.2
Submitted: (Oct 18, 2016)
Evidence details
Likely benign
(Mar 08, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000524478.4
Submitted: (Mar 26, 2018)
Evidence details
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
Likely benign
(Feb 13, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
PreventionGenetics,PreventionGenetics
Accession: SCV000852810.1
Submitted: (Oct 12, 2018)
Evidence details
Uncertain significance
(Dec 03, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000230813.5
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Likely benign
(May 03, 2018)
criteria provided, single submitter
Method: clinical testing
Minicore myopathy with external ophthalmoplegia
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000412519.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely benign
(May 03, 2018)
criteria provided, single submitter
Method: clinical testing
Central core myopathy
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000412522.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely benign
(May 03, 2018)
criteria provided, single submitter
Method: clinical testing
Malignant hyperthermia, susceptibility to, 1
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000412521.3
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (1)
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Benign
(Nov 30, 2020)
criteria provided, single submitter
Method: clinical testing
RYR1-Related Disorders
Allele origin: germline
Invitae
Accession: SCV000660050.5
Submitted: (Jan 07, 2021)
Evidence details
Likely benign
(Jun 01, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001151868.6
Submitted: (Jul 04, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Novel missense mutations and unexpected multiple changes of RYR1 gene in 75 malignant hyperthermia families. Tammaro A Clinical genetics 2011 PMID: 20681998
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RYR1 - - - -

Text-mined citations for rs142558977...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 10, 2021