GeneBe

COL6A1

collagen type VI alpha 1 chain, the group of Collagens

Basic information

Region (hg38): 21:45981770-46005050

Links

ENSG00000142156 ∙ NCBI:1291 ∙ OMIM:120220 ∙ HGNC:2211 ∙ Uniprot:P12109 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Bethlem myopathy 1A (Strong), mode of inheritance: AD
  • Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AD
  • Bethlem myopathy 1A (Strong), mode of inheritance: AR
  • Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AR
  • Bethlem myopathy (Supportive), mode of inheritance: AD
  • Ullrich congenital muscular dystrophy (Supportive), mode of inheritance: AD
  • Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AR
  • Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AD
  • collagen 6-related myopathy (Definitive), mode of inheritance: AD
  • collagen 6-related myopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ullrich congenital muscular dystrophy 1A; Bethlem myopathy 1AAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal963533; 3632670; 8782832; 11932968; 12840783; 12958705; 16130093; 15689448; 15955946; 17785674; 17886299; 18362356; 18366090; 19564581; 20301676; 20976770

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL6A1 gene.

  • Bethlem myopathy 1A (69 variants)
  • not provided (36 variants)
  • Ullrich congenital muscular dystrophy 1A (7 variants)
  • Abnormality of the musculature (2 variants)
  • ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1A, AUTOSOMAL DOMINANT (2 variants)
  • Collagen 6-related myopathy (2 variants)
  • COL6A1-related disorder (1 variants)
  • Inborn genetic diseases (1 variants)
  • Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL6A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
15
clinvar
197
clinvar
28
clinvar
 240
missense
26
clinvar
25
clinvar
293
clinvar
74
clinvar
53
clinvar
 471
nonsense
9
clinvar
2
clinvar
2
clinvar
 13
start loss
1
clinvar
 1
frameshift
15
clinvar
8
clinvar
5
clinvar
 28
inframe indel
1
clinvar
4
clinvar
10
clinvar
 15
splice donor/acceptor (+/-2bp)
32
clinvar
30
clinvar
4
clinvar
 66
splice region
3
1
60
48
4
 116
non coding
1
clinvar
1
clinvar
47
clinvar
302
clinvar
124
clinvar
 475
Total 84 70 377 573 205

Highest pathogenic variant AF is 0.0000131

Variants in COL6A1

This is a list of pathogenic ClinVar variants found in the COL6A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
21-45981775-G-A Collagen 6-related myopathy Uncertain significance (Jan 13, 2018)340305
21-45981786-C-G Collagen 6-related myopathy Benign (Jan 12, 2018)340306
21-45981811-C-T Collagen 6-related myopathy Benign (Jan 13, 2018)895551
21-45981832-G-A not specified Uncertain significance (Apr 08, 2024)3251454
21-45981843-C-A not specified Likely benign (-)258282
21-45981846-C-G not specified • Collagen 6-related myopathy Benign (Jan 12, 2018)93792
21-45981850-C-T Uncertain significance (Jun 18, 2021)499198
21-45981851-A-T Bethlem myopathy 1A Uncertain significance (Jul 19, 2022)1522832
21-45981855-G-A Bethlem myopathy 1A Uncertain significance (Feb 08, 2018)577490
21-45981859-G-A Bethlem myopathy 1A Likely benign (Dec 13, 2023)763549
21-45981859-G-T Uncertain significance (Jan 15, 2016)285351
21-45981860-G-A Bethlem myopathy 1A Uncertain significance (Jun 05, 2022)1394771
21-45981863-C-T Bethlem myopathy 1A Uncertain significance (Jul 05, 2022)1359474
21-45981864-G-A Bethlem myopathy 1A Uncertain significance (Jan 30, 2017)476415
21-45981865-T-A Bethlem myopathy 1A Likely benign (May 30, 2021)1451703
21-45981867-C-G Bethlem myopathy 1A Uncertain significance (Jul 06, 2022)2014767
21-45981869-C-A Bethlem myopathy 1A Uncertain significance (Nov 13, 2023)2088603
21-45981877-C-G Bethlem myopathy 1A Benign (Dec 21, 2023)2920525
21-45981886-G-C Bethlem myopathy 1A Likely benign (Aug 07, 2021)1576619
21-45981890-G-A Bethlem myopathy 1A Uncertain significance (Dec 09, 2021)1396686
21-45981893-T-C Uncertain significance (May 17, 2022)1800477
21-45981894-G-T Bethlem myopathy 1A Uncertain significance (Apr 24, 2022)2130400
21-45981896-T-C Bethlem myopathy 1A Uncertain significance (Dec 15, 2023)2784785
21-45981898-GAC-G Bethlem myopathy 1A Pathogenic (Aug 17, 2023)1457047
21-45981900-C-CAGCCGCGCAGGATG Bethlem myopathy 1A Pathogenic (Apr 12, 2023)803639

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
COL6A1protein_codingprotein_codingENST00000361866 3523314
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.000.00004661257100331257430.000131
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.5016446810.9460.00004946530
Missense in Polyphen213219.050.972372037
Synonymous-1.423433111.100.00002762074
Loss of Function6.45863.50.1260.00000346706

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003600.000356
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.0001470.000141
Middle Eastern0.000.00
South Asian0.0002290.000229
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Collagen VI acts as a cell-binding protein.;
Disease
DISEASE: Bethlem myopathy 1 (BTHLM1) [MIM:158810]: A benign proximal myopathy characterized by early childhood onset and joint contractures most frequently affecting the elbows and ankles. {ECO:0000269|PubMed:11865138, ECO:0000269|PubMed:15689448, ECO:0000269|PubMed:15955946, ECO:0000269|PubMed:8782832}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ullrich congenital muscular dystrophy 1 (UCMD1) [MIM:254090]: A congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy. {ECO:0000269|PubMed:15689448, ECO:0000269|PubMed:16130093, ECO:0000269|PubMed:17785674}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);miRNA targets in ECM and membrane receptors;PI3K-Akt Signaling Pathway;Developmental Biology;Assembly of collagen fibrils and other multimeric structures;Signal Transduction;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Signaling by PDGF;Collagen formation;Extracellular matrix organization;Integrin;NCAM signaling for neurite out-growth;NCAM1 interactions;Axon guidance;Signaling by Receptor Tyrosine Kinases;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis (Consensus)

Recessive Scores

pRec
0.540

Intolerance Scores

loftool
0.0443
rvis_EVS
-1.49
rvis_percentile_EVS
3.62

Haploinsufficiency Scores

pHI
0.641
hipred
Y
hipred_score
0.717
ghis
0.638

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.676

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyHighMediumHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Col6a1
Phenotype
muscle phenotype;

Zebrafish Information Network

Gene name
col6a1
Affected structure
skeletal muscle cell
Phenotype tag
abnormal
Phenotype quality
structure

Gene ontology

Biological process
osteoblast differentiation;growth plate cartilage chondrocyte morphogenesis;cell adhesion;extracellular matrix organization;endodermal cell differentiation;protein heterotrimerization;cellular response to amino acid stimulus
Cellular component
extracellular region;collagen type VI trimer;extracellular space;lysosomal membrane;endoplasmic reticulum lumen;membrane;extracellular matrix;protein-containing complex;sarcolemma;collagen-containing extracellular matrix;extracellular exosome
Molecular function
extracellular matrix structural constituent conferring tensile strength;platelet-derived growth factor binding