Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590567 | SCV000695531 | uncertain significance | not provided | 2016-11-17 | criteria provided, single submitter | clinical testing | Variant summary: The FBN1 c.4022A>G (p.Asn1341Ser) variant involves the alteration of a conserved nucleotide. This variant is located within the calcium-binding EGF-like domain and alters one of the three residues that compose the Ca2+ binding site (Handford_2000, McGettrick_2000). Calcium-binding cites are crucial for numerous protein-protein interactions, however, this particular alteration has yet to be functionally assessed. 3/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant has been reported in at least two patients with classical MFS and is absent from 121328 control chromosomes. Taken together, this variant is classified as VUS-Possibly Pathogenic. |
| Mendelics | RCV000989325 | SCV001139607 | likely pathogenic | Marfan syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001065647 | SCV001230616 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-06-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. ClinVar contains an entry for this variant (Variation ID: 495603). This missense change has been observed in individuals with clinical features of FBN1-related conditions (PMID: 10464652, 27611364, 31098894; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1341 of the FBN1 protein (p.Asn1341Ser). |
| 3billion, |
RCV000989325 | SCV002058149 | likely pathogenic | Marfan syndrome | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with FBN1 related disorder (ClinVar ID: VCV000495603, PS1_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.901, 3CNET: 0.769, PP3_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant is located in a well-established functional domain or exonic hotspot, where pathogenic variants have frequently reported (PM1_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Gene |
RCV000590567 | SCV005881980 | pathogenic | not provided | 2024-09-04 | criteria provided, single submitter | clinical testing | Identified in individuals with Marfan syndrome or ectopia lentis referred for genetic testing at GeneDx or in published literature (PMID: 10464652, 27611364, 31098894, 31536524); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27611364, 24941995, 11875032, 10464652, 31098894, 31536524, 35616356, 36729443, 20591885) |