ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.4511A>T (p.Asn1504Ile)

dbSNP: rs1555397209
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001201573 SCV001372649 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2020-10-05 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asn1504 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been observed in individuals with FBN1-related conditions (PMID: 27906200, Invitae), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual with clinical features of Marfan syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with isoleucine at codon 1504 of the FBN1 protein (p.Asn1504Ile). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and isoleucine.

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