Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002235905 | SCV000949028 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2022-09-24 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 653176). This variant has not been reported in the literature in individuals affected with COL5A2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 53 of the COL5A2 protein (p.Ile53Asn). |
| ARUP Laboratories, |
RCV001287497 | SCV001474192 | uncertain significance | Ehlers-Danlos syndrome, classic type, 2 | 2020-04-04 | criteria provided, single submitter | clinical testing | The COL5A2 c.158T>A; p.Ile53Asn variant (rs1443765130), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 653176). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The isoleucine at codon 53 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Ile53Asn variant is uncertain at this time. |
| Mayo Clinic Laboratories, |
RCV002261223 | SCV002542003 | uncertain significance | not provided | 2021-05-05 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002397660 | SCV002706780 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-07-26 | criteria provided, single submitter | clinical testing | The p.I53N variant (also known as c.158T>A), located in coding exon 2 of the COL5A2 gene, results from a T to A substitution at nucleotide position 158. The isoleucine at codon 53 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV001287497 | SCV002782191 | uncertain significance | Ehlers-Danlos syndrome, classic type, 2 | 2021-11-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002261223 | SCV003836816 | uncertain significance | not provided | 2023-02-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; HGMD) |