Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004021017 | SCV000319259 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-08 | criteria provided, single submitter | clinical testing | The c.2927T>C (p.V976A) alteration is located in exon 40 (coding exon 40) of the COL3A1 gene. This alteration results from a T to C substitution at nucleotide position 2927, causing the valine (V) at amino acid position 976 to be replaced by an alanine (A). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration was identified in a patient who presented with spontaneous coronary artery dissection (SCAD) and was included in a study to evaluate clinical features, family history, and genes associated with SCAD (Kaadan, 2018). This amino acid position is poorly conserved in available vertebrate species, and alanine is the reference amino acid in other vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000458398 | SCV000541801 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2022-01-01 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt COL3A1 protein function. ClinVar contains an entry for this variant (Variation ID: 263828). This missense change has been observed in individual(s) with spontaneous coronary artery dissection (PMID: 29650765). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 976 of the COL3A1 protein (p.Val976Ala). |
| Fulgent Genetics, |
RCV002503957 | SCV002816317 | uncertain significance | Ehlers-Danlos syndrome, type 4; Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome | 2021-09-22 | criteria provided, single submitter | clinical testing |