ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.2231C>T (p.Pro744Leu) (rs199504304)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726195 SCV000342813 uncertain significance not provided 2017-06-27 criteria provided, single submitter clinical testing
GeneDx RCV000726195 SCV000589896 uncertain significance not provided 2018-07-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL6A3 gene. The P744L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P744L variant is observed in 26/66,692 (0.04%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P744L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, 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. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000367426 SCV000428844 likely benign Collagen VI-related myopathy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000542766 SCV000657267 uncertain significance Bethlem myopathy 1 2018-09-14 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 744 of the COL6A3 protein (p.Pro744Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs199504304, ExAC 0.04%) but has not been reported in the literature in individuals with a COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 288643). 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 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.