VCV000029876.4 - ClinVar

NM_000540.2(RYR1):c.[5726_5727delAG;9242T>C]

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_000540.2(RYR1):c.[5726_5727delAG;9242T>C]

Other names: RYR1, 2-BP DEL, 5726AG AND MET3081THR
Functional consequence: -
Links: ClinGen: CA042813; OMIM: 180901.0035

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
RYR1		No evidence available	No evidence available	GRCh38 GRCh37	8949	9264

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Congenital multicore myopathy with external ophthalmoplegia	Pathogenic (1)	no assertion criteria provided	Nov 1, 2010	RCV000022757.13

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Nov 01, 2010)	no assertion criteria provided Method: literature only	CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000044046.4 First in ClinVar: Apr 04, 2013 Last updated: Jul 23, 2024	Publications: PubMed (1) PubMed: 20839240 Comment on evidence: In 1 South African patient (patient 1) with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; 255320), Wilmshurst et al. (2010) identified compound heterozygosity … (more) In 1 South African patient (patient 1) with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; 255320), Wilmshurst et al. (2010) identified compound heterozygosity for 2 alleles containing complex mutations in the RYR1 gene: 1 allele carried a 2-bp deletion (5726delAG) in exon 35 and a 9242T-C transition in exon 63, resulting in a met3081-to-thr (M3081T) substitution, and the other allele carried a splice site mutation and a V4842M substitution (180901.0036). The 2-bp del/M3081T allele was also found in patient 12, also South African, in whom a mutation on the second allele was not identified. Haplotype analysis indicated a founder effect in the South African population. The phenotype was characterized by onset at birth, neonatal hypotonia and weakness, delayed motor development, external ophthalmoplegia, and bulbar involvement. Histopathologic findings included central nuclei, multiple internalized nuclei, type 1 fiber predominance and hypotrophy, relative type 2 hypertrophy, and oxidative abnormalities in electron microscopic analysis, although frank cores were not typically seen. (less)

Germline Functional Evidence

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 germline classification of this variant

Title	Author	Journal	Year	Link
Using exome data to identify malignant hyperthermia susceptibility mutations.	Gonsalves SG	Anesthesiology	2013	PMID: 24195946
RYR1 mutations are a common cause of congenital myopathies with central nuclei.	Wilmshurst JM	Annals of neurology	2010	PMID: 20839240
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RYR1	-	-	-	-

Text-mined citations for this variant ...

Record last updated Nov 30, 2024

ClinVar Genomic variation as it relates to human health

NM_000540.2(RYR1):c.[5726_5727delAG;9242T>C]

Variant Details

NM_000540.2(RYR1):c.[5726_5727delAG;9242T>C]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...