Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CSER _CC_NCGL, |
RCV000210901 | SCV000264599 | likely benign | Ehlers-Danlos syndrome, type 4 | 2015-12-01 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV000210901 | SCV000541798 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-02-21 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1209 of the COL3A1 protein (p.Gly1209Ala). This variant is present in population databases (rs374452484, gnomAD 0.004%). ClinVar contains an entry for this variant (Variation ID: 225283). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Color Diagnostics, |
RCV000772065 | SCV000905094 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-11-18 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with alanine at codon 1209 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has been identified in 7/251388 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Gene |
RCV001753633 | SCV001987660 | uncertain significance | not provided | 2020-08-20 | criteria provided, single submitter | clinical testing | 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 (Stenson et al., 2014) |
All of Us Research Program, |
RCV000210901 | SCV004824948 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2024-03-24 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with alanine at codon 1209 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 7/251388 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |