ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.1417C>T (p.Arg473Trp)

gnomAD frequency: 0.00001  dbSNP: rs767068276
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001182190 SCV001347547 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-02-28 criteria provided, single submitter clinical testing This missense variant replaces cysteine and arginine with tyrosine and tryptophan at codon 472 and 473 of the FBN1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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 RCV002559017 SCV003024044 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-04-20 criteria provided, single submitter clinical testing 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 expected to disrupt FBN1 protein function. ClinVar contains an entry for this variant (Variation ID: 922251). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This variant is present in population databases (rs767068276, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 473 of the FBN1 protein (p.Arg473Trp).
All of Us Research Program, National Institutes of Health RCV004008284 SCV004840154 uncertain significance Marfan syndrome 2023-12-01 criteria provided, single submitter clinical testing

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