Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000478360 | SCV000568538 | pathogenic | not provided | 2022-09-12 | criteria provided, single submitter | clinical testing | Functional studies using an inducible expression system for expressing p.(R989C) showed that even a small amount of the R989C mutant collagen would induce aberrations in the cell/matrix systems (Jensen et al., 2011); Located in the triple helical domain, a region of the protein in which cysteine residues are typically excluded (HGMD); 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: 16155195, 9101290, 35250876, 25735649, 8325895, 21924244, 15895462, 7752132, 29354277, 21472893) |
Fulgent Genetics, |
RCV000762895 | SCV000893295 | pathogenic | Achondrogenesis type II; Avascular necrosis of femoral head, primary, 1; Multiple epiphyseal dysplasia, Beighton type; Legg-Calve-Perthes disease; Kniest dysplasia; Namaqualand hip dysplasia; Spondyloperipheral dysplasia; Stickler syndrome type 1; Platyspondylic dysplasia, Torrance type; Spondylometaphyseal dysplasia; Spondyloepiphyseal dysplasia congenita; Spondyloepiphyseal dysplasia with metatarsal shortening; Stickler syndrome, type I, nonsyndromic ocular; Spondyloepiphyseal dysplasia, Stanescu type | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics Munich, |
RCV000995718 | SCV001150043 | pathogenic | Spondyloperipheral dysplasia | 2019-05-27 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000478360 | SCV001581179 | pathogenic | not provided | 2024-11-11 | 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 989 of the COL2A1 protein (p.Arg989Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant spondyloepiphyseal dysplasia congenita (PMID: 8325895, 21924244, 25735649). It has also been observed to segregate with disease in related individuals. This variant is also known as R789C. ClinVar contains an entry for this variant (Variation ID: 17366). 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 COL2A1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects COL2A1 function (PMID: 21472893). For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV000478360 | SCV001832237 | pathogenic | not provided | 2017-12-27 | criteria provided, single submitter | clinical testing | |
3billion | RCV005252114 | SCV002058184 | pathogenic | Spondyloperipheral dysplasia; Spondyloepiphyseal dysplasia, Stanescu type | 2024-02-20 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.95 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.73 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000017366 /PMID: 8325895 /3billion dataset). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 21924244, 25735649, 8325895). The variant has been reported to co-segregate with the disease in at least 3 similarly affected relatives/individuals in the same family or similarly affected unrelated families (PMID: 21924244). A different missense change at the same codon (p.Arg989Gly) has been reported to be associated with COL2A1 related disorder (PMID: 33908178). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
Ce |
RCV000478360 | SCV002497588 | pathogenic | not provided | 2022-02-01 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV000995718 | SCV002578929 | pathogenic | Spondyloperipheral dysplasia | 2022-06-14 | criteria provided, single submitter | clinical testing | |
Suma Genomics | RCV000018910 | SCV004037036 | likely pathogenic | Spondyloepiphyseal dysplasia congenita | criteria provided, single submitter | clinical testing | ||
Baylor Genetics | RCV000018910 | SCV005049425 | pathogenic | Spondyloepiphyseal dysplasia congenita | 2024-03-26 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000018910 | SCV000039194 | pathogenic | Spondyloepiphyseal dysplasia congenita | 1997-01-01 | no assertion criteria provided | literature only | |
Kasturba Medical College, |
RCV000018910 | SCV002569961 | pathogenic | Spondyloepiphyseal dysplasia congenita | no assertion criteria provided | clinical testing |