ClinVar Miner

Submissions for variant NM_000089.3(COL1A2):c.671G>A (p.Arg224His) (rs771139732)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000764735 SCV000895870 uncertain significance Osteogenesis imperfecta with normal sclerae, dominant form; Postmenopausal osteoporosis; Osteogenesis imperfecta, recessive perinatal lethal; Osteogenesis imperfecta type III; Ehlers-Danlos syndrome, autosomal recessive, cardiac valvular form; EHLERS-DANLOS SYNDROME, ARTHROCHALASIA TYPE, 2 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000631534 SCV000752616 uncertain significance Ehlers-Danlos syndrome, classic type; Osteogenesis imperfecta type I 2018-04-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 224 of the COL1A2 protein (p.Arg224His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs771139732, ExAC 0.05%). This variant has been reported in an individual affected with osteogenesis imperfecta (PMID: 26604951). However, in that individual, a pathogenic allele was also identified in COL1A1, which suggests that this c.671G>A variant was not the primary cause of disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. 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.