ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.5513G>A (p.Gly1838Asp)

dbSNP: rs78970689
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181546 SCV000233849 pathogenic not provided 2014-05-07 criteria provided, single submitter clinical testing p.Gly1838Asp (GGC>GAC): c.5513 G>A in exon 45 of the FBN1 gene (NM_000138.4)While the G1838D mutation in the FBN1 gene has not been reported to our knowledge, a mutation affecting this same residue, G1838C, has been reported in association with Marfan syndrome (Ganesh A et al., 2006). Additionally, mutations in nearby residues (C1835F, C1835Y, P1837S, C1847W, C1847R) have been reported in association with Marfan syndrome, further supporting the functional importance of this residue and this region of the protein. G1838D results in a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this mutation is damaging to the protein structure/function. Furthermore, G1838D 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.In summary, G1838D in the FBN1 gene is interpreted as a likely disease-causing mutation. The variant is found in TAAD panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000632002 SCV000753105 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2021-12-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly1838 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been observed in individuals with FBN1-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. 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: 200065). This missense change has been observed in individuals with Marfan syndrome (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1838 of the FBN1 protein (p.Gly1838Asp).
Revvity Omics, Revvity RCV000181546 SCV003833996 uncertain significance not provided 2021-12-09 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.