Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000181587 | SCV000233890 | uncertain significance | not provided | 2014-01-12 | criteria provided, single submitter | clinical testing | p.Ile2350Val (ATC>GTC): c.7048 A>G in exon 58 of the FBN1 gene (NM_000138.4)The I2350V variant in the FBN1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The I2350V variant is a conservative amino acid substitution as these residues share similar properties, and are least likely to impact secondary structure. The I2350 residue is conserved through mammals in evolution. In silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function.. Nevertheless, the I2350V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.With the clinical and molecular information available at this time, we cannot definitively determine if I2350V is a disease-causing mutation or a rare benign variant.The variant is found in TAAD panel(s). |
| Labcorp Genetics |
RCV000469404 | SCV000544871 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-11-15 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003996695 | SCV004823180 | uncertain significance | Marfan syndrome | 2024-01-03 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 2350 of the FBN1 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 1/250852 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. |
| Clinical Molecular Genetics Laboratory, |
RCV000584375 | SCV000692229 | uncertain significance | Loeys-Dietz syndrome | 2017-03-30 | no assertion criteria provided | clinical testing |