Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000545342 | SCV000631628 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-05-08 | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL3A1 protein function. ClinVar contains an entry for this variant (Variation ID: 459765). This missense change has been observed in individual(s) with clinical features of Ehlers-Danlos syndrome (Invitae). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 509 of the COL3A1 protein (p.Arg509Cys). |
| Color Diagnostics, |
RCV003528188 | SCV004361474 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-11-22 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 509 of the COL3A1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 2/195272 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. |