ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.4523G>T (p.Ser1508Ile)

dbSNP: rs1555397207
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002314355 SCV000738884 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-04-08 criteria provided, single submitter clinical testing The p.S1508I variant (also known as c.4523G>T), located in coding exon 36 of the FBN1 gene, results from a G to T substitution at nucleotide position 4523. The serine at codon 1508 is replaced by isoleucine, an amino acid with dissimilar properties, and is located in the cb EGF-like #22 domain. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001855276 SCV002144943 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-07-13 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: 519764). This missense change has been observed in individual(s) with clinical features of FBN1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1508 of the FBN1 protein (p.Ser1508Ile).
All of Us Research Program, National Institutes of Health RCV004002725 SCV004821046 uncertain significance Marfan syndrome 2023-03-28 criteria provided, single submitter clinical testing

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