NM_001848.3(COL6A1):c.971_979del (p.Lys324_Gly326del) AND Bethlem myopathy 1A

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 31, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002017566.4

Allele description [Variation Report for NM_001848.3(COL6A1):c.971_979del (p.Lys324_Gly326del)]

NM_001848.3(COL6A1):c.971_979del (p.Lys324_Gly326del)

Gene:

COL6A1:collagen type VI alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_001848.3(COL6A1):c.971_979del (p.Lys324_Gly326del)

HGVS:

NC_000021.9:g.45990391_45990399del
NG_008674.1:g.13643_13651del
NM_001848.3:c.971_979delMANE SELECT
NP_001839.2:p.Lys324_Gly326del
LRG_475:g.13643_13651del
NC_000021.8:g.47410301_47410309del
NC_000021.8:g.47410305_47410313del

Links:

dbSNP: rs2123472068

NCBI 1000 Genomes Browser:

rs2123472068

Molecular consequence:

NM_001848.3:c.971_979del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Bethlem myopathy 1A
Synonyms:: Myopathy, benign congenital, with contractures; Bethlem myopathy 1
Identifiers:: MONDO: MONDO:0024530; MedGen: CN029274; Orphanet: 610; OMIM: 158810

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002291999	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 31, 2021)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 7695699, 8218237, 19344236, 15689448, 24038877, 17785673, 34167565, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002291999

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 31, 2021)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution.

Bella J, Eaton M, Brodsky B, Berman HM.

Science. 1994 Oct 7;266(5182):75-81.

PubMed [citation]

PMID:: 7695699

Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence.

Long CG, Braswell E, Zhu D, Apigo J, Baum J, Brodsky B.

Biochemistry. 1993 Nov 2;32(43):11688-95.

PubMed [citation]

PMID:: 8218237

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002291999.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the triple helix domain of COL6A1. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL6A1, variants at these glycine residues are significantly enriched in individuals with autosomal dominant disease (PMID: 15689448, 24038877) compared to the general population (ExAC). This variant is also known as c.967_975del9 (p.Gly323_Lys325del). This variant has been observed in individual(s) with autosomal dominant COL6A1-related conditions (PMID: 17785673, 34167565). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This variant, c.971_979del, results in the deletion of 3 amino acid(s) of the COL6A1 protein (p.Lys324_Gly326del), but otherwise preserves the integrity of the reading frame.

#	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

Last Updated: Sep 29, 2024

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