ClinVar Miner

Submissions for variant NM_000088.4(COL1A1):c.4196G>A (p.Arg1399His)

gnomAD frequency: 0.00004  dbSNP: rs146035171
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521165 SCV000618736 uncertain significance not provided 2024-12-26 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD)
Fulgent Genetics, Fulgent Genetics RCV000765368 SCV000896633 uncertain significance Osteogenesis imperfecta with normal sclerae, dominant form; Postmenopausal osteoporosis; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Infantile cortical hyperostosis; Ehlers-Danlos syndrome, arthrochalasia type; Osteogenesis imperfecta type I 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000792484 SCV000931786 benign Osteogenesis imperfecta type I 2024-12-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002329239 SCV002627078 uncertain significance Cardiovascular phenotype 2019-01-11 criteria provided, single submitter clinical testing The p.R1399H variant (also known as c.4196G>A), located in coding exon 50 of the COL1A1 gene, results from a G to A substitution at nucleotide position 4196. The arginine at codon 1399 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Johns Hopkins Genomics, Johns Hopkins University RCV000521165 SCV003839075 uncertain significance not provided 2023-01-20 criteria provided, single submitter clinical testing This COl1A1 missense variant (rs146035171 ) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 8/282306 total alleles; 0.003%; no homozygotes). It has been reported in ClinVar (Variation ID 450185), but to our knowledge, has not been reported in individuals with COL1A1-related disorders in the literature. Two bioinformatic tools queried predict that this substitution would be damaging, but these algorithms have low specificity, especially for predicting gain of function or dominant negative variants. The arginine residue at this position is evolutionarily conserved across most of the species assessed. We consider the clinical significance of c.4196G>A;p.Arg1399His in COL1A1 to be uncertain at this time.
Fulgent Genetics, Fulgent Genetics RCV005027609 SCV005649546 uncertain significance Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Infantile cortical hyperostosis; Ehlers-Danlos syndrome, arthrochalasia type; Osteogenesis imperfecta type I; Osteoporosis; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 2024-01-23 criteria provided, single submitter clinical testing

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.