VCV000029642.3 - ClinVar

NM_001849.3(COL6A2):c.[2489G>A;2527C>T]

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_001849.3(COL6A2):c.[2489G>A;2527C>T]

Other names: COL6A2, ARG830GLN AND ARG843TRP
Functional consequence: -
Links: ClinGen: CA042778; OMIM: 120240.0017

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.
COL6A2		-	-	GRCh38 GRCh37	2044	2183

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.
BETHLEM MYOPATHY 1B, AUTOSOMAL RECESSIVE	Pathogenic (1)	no assertion criteria provided	Dec 1, 2009	RCV003764620.2

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 (Dec 01, 2009)	no assertion criteria provided Method: literature only	BETHLEM MYOPATHY 1B, AUTOSOMAL RECESSIVE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000043779.5 First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2024	Publications: PubMed (2) PubMed: 19949035‚ 18852439 Comment on evidence: In a 25-year-old woman with Bethlem myopathy (BTHLM1B; 620725), Gualandi et al. (2009) identified compound heterozygosity for variations in the COL6A2 gene. The maternal allele … (more) In a 25-year-old woman with Bethlem myopathy (BTHLM1B; 620725), Gualandi et al. (2009) identified compound heterozygosity for variations in the COL6A2 gene. The maternal allele carried a 2571G-A and a 2609C-T transition, both in exon 28, resulting in an arg830-to-gln (R830Q) and an arg843-to-trp (R843W) substitution, respectively, in the C2 domain. Both mutations affected highly conserved residues. The paternal allele carried a Q819X (120240.0011) substitution. The patient had onset of progressive proximal muscle weakness at age 2 years. During the course of the disorder, she developed prominent joint contractures and decreased forced vital capacity (65% of predicted), but retained independent ambulation. Muscle biopsy showed a myopathic pattern and fibrosis with mildly decreased collagen VI staining. Studies of fibroblasts showed absence of collagen VI tetramer formation, but electron microscopy showed correct filamentous and interconnected collagen VI microfilaments. Gualandi et al. (2009) concluded that this woman showed rare autosomal recessive inheritance of Bethlem myopathy based on her genotype. However, the authors noted that the R819X mutation escaped nonsense-mediated decay and was thought not to be pathogenic in the heterozygous state, based on the report of Merlini et al. (2008). The fact that the woman reported by Gualandi et al. (2009) carried COL6A2 mutations on both alleles had implications for genetic counseling. (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
Panel-Based Exome Sequencing for Neuromuscular Disorders as a Diagnostic Service.	Westra D	Journal of neuromuscular diseases	2019	PMID: 31127727
Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients.	Nallamilli BRR	Annals of clinical and translational neurology	2018	PMID: 30564623
Genetic and clinical findings in a Chinese cohort of patients with collagen VI-related myopathies.	Fan Y	Clinical genetics	2018	PMID: 29419890
Natural history of pulmonary function in collagen VI-related myopathies.	Foley AR	Brain : a journal of neurology	2013	PMID: 24271325
Autosomal recessive Bethlem myopathy.	Gualandi F	Neurology	2009	PMID: 19949035
Autosomal recessive Bethlem myopathy.	Gualandi F	Neurology	2009	PMID: 19949035
Autosomal recessive Bethlem myopathy.	Gualandi F	Neurology	2009	PMID: 19949035
Autosomal recessive inheritance of classic Bethlem myopathy.	Foley AR	Neuromuscular disorders : NMD	2009	PMID: 19884007
Autosomal recessive myosclerosis myopathy is a collagen VI disorder.	Merlini L	Neurology	2008	PMID: 18852439
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=COL6A2	-	-	-	-
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=COL6A2	-	-	-	-
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Text-mined citations for this variant ...

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_001849.3(COL6A2):c.[2489G>A;2527C>T]

Variant Details

NM_001849.3(COL6A2):c.[2489G>A;2527C>T]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...