ClinVar Miner

Submissions for variant NM_000088.4(COL1A1):c.4328C>T (p.Ala1443Val)

dbSNP: rs1131692326
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
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV000496049 SCV000584182 likely pathogenic Osteogenesis imperfecta type I 2024-05-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000496049 SCV000962312 pathogenic Osteogenesis imperfecta type I 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1443 of the COL1A1 protein (p.Ala1443Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of osteogenesis imperfecta and/or osteogenesis imperfecta (PMID: 30614853, 33939306; Invitae). ClinVar contains an entry for this variant (Variation ID: 431035). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL1A1 protein function. For these reasons, this variant has been classified as Pathogenic.
MGZ Medical Genetics Center RCV000496049 SCV002579637 likely pathogenic Osteogenesis imperfecta type I 2022-06-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004737564 SCV005355789 likely pathogenic COL1A1-related disorder 2024-08-15 no assertion criteria provided clinical testing The COL1A1 c.4328C>T variant is predicted to result in the amino acid substitution p.Ala1443Val. This variant was reported in three individuals with osteogenesis imperfecta (Li et al. 2019. PubMed ID: 30614853; Higuchi et al. 2021. PubMed ID: 33939306). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as likely pathogenic.

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.