Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV001253430 | SCV001429135 | uncertain significance | Marfan syndrome | 2023-03-29 | criteria provided, single submitter | clinical testing | Criteria applied: pm2_sup, pp2 |
| Labcorp Genetics |
RCV003770318 | SCV004575912 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-02-09 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV001253430 | SCV004814748 | uncertain significance | Marfan syndrome | 2023-09-04 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 1417 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 2/251436 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. |
| Neuberg Centre For Genomic Medicine, |
RCV004546623 | SCV005042959 | uncertain significance | Weill-Marchesani syndrome 2, dominant | criteria provided, single submitter | clinical testing | The missense c.4250A>G p.Asn1417Ser variant in FBN1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn1417Ser variant is reported with an allele frequency of 0.0008% in the gnomAD exomes database and is novel not in any individuals in 1000 Genomes database. This variant has been reported to the ClinVar database as Likely Pathogenic, but no details are available for independent assessment. The amino acid change p.Asn1417Ser in FBN1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Asn at position 1417 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance VUS. Variants in FBN1 gene are also associated with Acromicric dysplasia, Familial Ectopia lentis, Geleophysic dysplasia 2, Marfan lipodystrophy syndrome, Marfan syndrome, and MASS syndrome with autosomal dominant inheritance. |