ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.988G>A (p.Asp330Asn) (rs139399166)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724011 SCV000224897 uncertain significance not provided 2017-04-27 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000407691 SCV000436665 likely benign Myosclerosis 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000311316 SCV000436666 likely benign Collagen VI-related myopathy 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000173749 SCV000618231 uncertain significance not specified 2017-07-24 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL6A2 gene. The D330N variant in the COL6A2 gene has been reported previously in an individual with macular degeneration with no reported history of muscle disease (Seddon et al., 2013). The D330N variant is observed in 32/65,228 (0.05%) alleles from individuals of European (non-Finnish) background in the ExAC dataset (Lek et al., 2016). The D330N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with COL6A2-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000536085 SCV000657235 uncertain significance Bethlem myopathy 1 2018-07-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 330 of the COL6A2 protein (p.Asp330Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs139399166, ExAC 0.05%) but has not been reported in the literature in individuals with a COL6A2-related disease. ClinVar contains an entry for this variant (Variation ID: 193634). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.