NM_004369.4(COL6A3):c.6212G>A (p.Gly2071Asp) AND Bethlem myopathy 1

Clinical significance:Likely pathogenic (Last evaluated: Aug 24, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000396169.4

Allele description [Variation Report for NM_004369.4(COL6A3):c.6212G>A (p.Gly2071Asp)]

NM_004369.4(COL6A3):c.6212G>A (p.Gly2071Asp)

Gene:
COL6A3:collagen type VI alpha 3 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q37.3
Genomic location:
Preferred name:
NM_004369.4(COL6A3):c.6212G>A (p.Gly2071Asp)
HGVS:
  • NC_000002.12:g.237360158C>T
  • NG_008676.1:g.59050G>A
  • NM_004369.4:c.6212G>AMANE SELECT
  • NM_057166.5:c.4391G>A
  • NM_057167.4:c.5594G>A
  • NP_004360.2:p.Gly2071Asp
  • NP_004360.2:p.Gly2071Asp
  • NP_476507.3:p.Gly1464Asp
  • NP_476508.2:p.Gly1865Asp
  • LRG_473t1:c.6212G>A
  • LRG_473:g.59050G>A
  • LRG_473p1:p.Gly2071Asp
  • NC_000002.11:g.238268801C>T
  • NM_004369.3:c.6212G>A
Protein change:
G1464D
Links:
dbSNP: rs886043737
NCBI 1000 Genomes Browser:
rs886043737
Molecular consequence:
  • NM_004369.4:c.6212G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057166.5:c.4391G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057167.4:c.5594G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Bethlem myopathy 1 (BTHLM1)
Synonyms:
Myopathy, benign congenital, with contractures; Muscular dystrophy, benign congenital; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 5
Identifiers:
MONDO: MONDO:0024530; MedGen: CN029274; Orphanet: 610; OMIM: 158810

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000657369Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 24, 2017)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Collagen structure and stability.

Shoulders MD, Raines RT.

Annu Rev Biochem. 2009;78:929-58. doi: 10.1146/annurev.biochem.77.032207.120833. Review.

PubMed [citation]
PMID:
19344236
PMCID:
PMC2846778
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000657369.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces glycine with aspartic acid at codon 2071 of the COL6A3 protein (p.Gly2071Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 287817). 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 COL6A3, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 15689448, 24038877) compared to the general population (ExAC). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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