Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001187545 | SCV000738554 | benign | Familial thoracic aortic aneurysm and aortic dissection | 2017-07-20 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Color Diagnostics, |
RCV001187545 | SCV001354365 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2019-02-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549742 | SCV001769951 | uncertain significance | not provided | 2021-02-16 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 519615; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Stenson et al., 2014) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797764 | SCV002041877 | uncertain significance | not specified | 2023-03-27 | criteria provided, single submitter | clinical testing | Variant summary: COL3A1 c.4273A>G (p.Ser1425Gly) results in a non-conservative amino acid change located in the Fibrillar collagen, C-terminal domain (IPR000885) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251360 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.4273A>G in individuals affected with Ehlers-Danlos Syndrome, Vascular Type and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as benign/likely benign (n=2) and as uncertain significance (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Invitae | RCV001868118 | SCV002308403 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1425 of the COL3A1 protein (p.Ser1425Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 519615). 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 not expected to disrupt COL3A1 protein function with a negative 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. |