ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.4259G>A (p.Ser1420Asn)

gnomAD frequency: 0.00004  dbSNP: rs751406554
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000799155 SCV000938806 uncertain significance Congenital contractural arachnodactyly 2023-08-14 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with thoracic aortic dilation (Invitae). 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. 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 not expected to disrupt FBN2 protein function. ClinVar contains an entry for this variant (Variation ID: 645128). This variant is present in population databases (rs751406554, gnomAD 0.004%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1420 of the FBN2 protein (p.Ser1420Asn).
GeneDx RCV001556932 SCV001778604 uncertain significance not provided 2020-10-20 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 645128; Landrum et al., 2016)
Ambry Genetics RCV002332618 SCV002627718 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-10-31 criteria provided, single submitter clinical testing The p.S1420N variant (also known as c.4259G>A), located in coding exon 33 of the FBN2 gene, results from a G to A substitution at nucleotide position 4259. The serine at codon 1420 is replaced by asparagine, an amino acid with highly similar properties, and is located in the cbEGF-like #20 domain. This amino acid position is not well conserved in available vertebrate species, and asparagine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001556932 SCV003834027 uncertain significance not provided 2021-11-12 criteria provided, single submitter clinical testing

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