Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| MGZ Medical Genetics Center | RCV000017895 | SCV002579946 | likely pathogenic | Marfan syndrome | 2022-05-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002426510 | SCV002729213 | likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2021-03-26 | criteria provided, single submitter | clinical testing | The p.D723A variant (also known as c.2168A>C), located in coding exon 18 of the FBN1 gene, results from an A to C substitution at nucleotide position 2168. This variant impacts the first base pair of coding exon 18. The aspartic acid at codon 723 is replaced by alanine, an amino acid with dissimilar properties, and is located in the cbEGF-like #7 domain. This variant was detected as a de novo heterozygous variant in an individual who met clinical criteria for Marfan syndrome (Dietz HC et al. Genomics, 1993 Aug;17:468-75). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Invitae | RCV003764583 | SCV004570995 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 723 of the FBN1 protein (p.Asp723Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Marfan syndrome (PMID: 8406497). In at least one individual the variant was observed to be de novo. This variant is also known as D-176A. ClinVar contains an entry for this variant (Variation ID: 16433). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Asp723 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12203987). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000017895 | SCV000038174 | pathogenic | Marfan syndrome | 1992-05-01 | no assertion criteria provided | literature only |