ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.6595G>A (p.Gly2199Ser)

gnomAD frequency: 0.00001  dbSNP: rs770132403
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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 RCV000697791 SCV000826422 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2018-08-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2199 of the FBN1 protein (p.Gly2199Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs770132403, ExAC 0.006%). This variant has been observed in an individual with aortic dissection (PMID: 28973303). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
AiLife Diagnostics, AiLife Diagnostics RCV002223916 SCV002503170 uncertain significance not provided 2021-12-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003999672 SCV004840108 uncertain significance Marfan syndrome 2024-08-08 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV005402964 SCV006064112 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-09-24 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 2199 of the FBN1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with thoracic aortic aneurysm (Gillis 2019, doctoral thesis at the University of Antwerp, Belgium) and in an individual suspected of having Marfan syndrome, who also carried a variant of uncertain significance in the FBN2 gene (PMID: 31506931). This variant has been identified in 3/251244 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.

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