ClinVar Miner

Submissions for variant NM_080680.3(COL11A2):c.1999G>A (p.Gly667Ser)

gnomAD frequency: 0.00001  dbSNP: rs1322629595
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
GeneDx RCV001591459 SCV001815388 uncertain significance not provided 2022-06-24 criteria provided, single submitter clinical testing Identified in a patient with epileptic encephalopathy (EE) or developmental and epileptic encephalopathy (DEE) who also harbored a pathogenic variant in the SYNGAP1 gene (Takata et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31175295)
Labcorp Genetics (formerly Invitae), Labcorp RCV001591459 SCV002268845 uncertain significance not provided 2024-12-09 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 667 of the COL11A2 protein (p.Gly667Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL11A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1213287). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt COL11A2 protein function with a positive predictive value of 95%. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587189 SCV005076447 uncertain significance not specified 2024-04-25 criteria provided, single submitter clinical testing Variant summary: COL11A2 c.1999G>A (p.Gly667Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246156 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1999G>A in individuals affected with COL11A2-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1213287). Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV005038269 SCV005669019 likely pathogenic Autosomal recessive nonsyndromic hearing loss 53; Autosomal dominant nonsyndromic hearing loss 13; Otospondylomegaepiphyseal dysplasia, autosomal recessive; Otospondylomegaepiphyseal dysplasia, autosomal dominant; Fibrochondrogenesis 2 2024-05-03 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.