ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.2140G>A (p.Gly714Arg)

dbSNP: rs1566912644
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001035646 SCV001198980 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-05-26 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 714 of the FBN1 protein (p.Gly714Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of FBN1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 834873). 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 with a positive predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Ambry Genetics RCV005338504 SCV006002740 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2025-01-14 criteria provided, single submitter clinical testing The p.G714R variant (also known as c.2140G>A), located in coding exon 17 of the FBN1 gene, results from a G to A substitution at nucleotide position 2140. The glycine at codon 714 is replaced by arginine, an amino acid with dissimilar properties. 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 available evidence, the clinical significance of this variant remains unclear.

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