Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001050723 | SCV001214844 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2021-04-17 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FBN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with alanine at codon 1583 of the FBN1 protein (p.Ser1583Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. |
| Ambry Genetics | RCV002339255 | SCV002639413 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-10-15 | criteria provided, single submitter | clinical testing | The p.S1583A variant (also known as c.4747T>G), located in coding exon 37 of the FBN1 gene, results from a T to G substitution at nucleotide position 4747. The amino acid change results in serine to alanine at codon 1583, an amino acid with similar properties. However, this change occurs in the last base pair of coding exon 37, which makes it likely to have some effect on normal mRNA splicing. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |