Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000181089 | SCV000233365 | uncertain significance | not provided | 2012-12-11 | criteria provided, single submitter | clinical testing | p.Gln641Glu (CAA>GAA): c.1921 C>G in exon 27 of the COL3A1 gene (NM_000090.3).The Gln641Glu variant in the COL3A1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The Gln641Glu vas was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project reports, indicating it is not a common benign variant in these populations. Gln641Glu results in a semi-conservative amino acid substitution of a neutral, polar Glutamine with a negatively charged Glutamic acid at a position that is conserved until chicken. Mutations in nearby residues located in the Gly-X-Y repeat region (Gly636Arg, Gly639Val, Gly642Asp) have been reported in association with Ehlers Danlos syndrome, supporting the functional importance of this region of the protein. With the clinical and molecular information available at this time, we cannot definitively determine if Gln641Glu is a disease-causing mutation or a rare benign variant. The variant is found in TAAD panel(s). |
Color Diagnostics, |
RCV001804910 | SCV002053506 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-04-19 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with glutamic acid at codon 641 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 cardiovascular disorders in the literature. This variant has been identified in 1/251042 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. |
Fulgent Genetics, |
RCV002492797 | SCV002784025 | uncertain significance | Ehlers-Danlos syndrome, type 4; Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome | 2021-08-13 | criteria provided, single submitter | clinical testing |