ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.5876A>G (p.Asn1959Ser)

gnomAD frequency: 0.00001  dbSNP: rs773486280
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001187082 SCV001353746 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 1959 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/250888 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001221334 SCV001393374 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-09-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002497649 SCV002777557 uncertain significance Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome 2021-09-03 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004008664 SCV004814622 uncertain significance Marfan syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 1959 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/250888 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001187082 SCV005032635 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-11-13 criteria provided, single submitter clinical testing The p.N1959S variant (also known as c.5876A>G), located in coding exon 47 of the FBN1 gene, results from an A to G substitution at nucleotide position 5876. The asparagine at codon 1959 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well conserved in available 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.

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