ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.209G>T (p.Gly70Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002424179 SCV002730358 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-05-13 criteria provided, single submitter clinical testing The p.G70V variant (also known as c.209G>T), located in coding exon 2 of the FBN1 gene, results from a G to T substitution at nucleotide position 209. The glycine at codon 70 is replaced by valine, an amino acid with dissimilar properties. This variant has been detected in an individual with aortic dissection from a non-syndromic thoracic aortic aneurysm and dissection cohort (Guo J et al. Sci Rep, 2015 Aug;5:13115). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003101054 SCV003442977 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 70 of the FBN1 protein (p.Gly70Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with thoracic aortic aneurysm and dissection (PMID: 26272055). ClinVar contains an entry for this variant (Variation ID: 1785867). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FBN1 protein function with a positive predictive value of 95%. 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.

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