Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000429567 | SCV000536135 | uncertain significance | not provided | 2018-03-28 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the COL11A2 gene. The G1048S variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed in the Exome Aggregation Consortium or in approximately 4,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G1048S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with disease (Stenson et al., 2014), indicating that this region of the gene is not known to harbor disease-causing variants. |
| Fulgent Genetics, |
RCV005044647 | SCV005669009 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 53; Autosomal dominant nonsyndromic hearing loss 13; Otospondylomegaepiphyseal dysplasia, autosomal recessive; Otospondylomegaepiphyseal dysplasia, autosomal dominant; Fibrochondrogenesis 2 | 2024-03-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000429567 | SCV005734097 | uncertain significance | not provided | 2024-11-19 | 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 1048 of the COL11A2 protein (p.Gly1048Ser). 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: 392807). 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. |