ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.3397C>T (p.Arg1133Cys)

gnomAD frequency: 0.00001  dbSNP: rs1938732355
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV002227901 SCV002507173 uncertain significance Spondyloepiphyseal dysplasia congenita 2022-05-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003101301 SCV002951268 likely pathogenic not provided 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1133 of the COL2A1 protein (p.Arg1133Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive spondyloepiphyseal dysplasia (PMID: 31755234). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1679885). 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 COL2A1 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GenomeConnect, ClinGen RCV003093905 SCV003761499 not provided Achondrogenesis type II; Kniest dysplasia; Stickler syndrome type 1; Platyspondylic dysplasia, Torrance type; Spondyloepiphyseal dysplasia congenita; Spondyloepiphyseal dysplasia with metatarsal shortening; Osteoarthritis; Spondyloepimetaphyseal dysplasia, Strudwick type no assertion provided phenotyping only Variant classified as Uncertain significance and reported on 12-10-2021 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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.