ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.164G>A (p.Gly55Glu)

dbSNP: rs2140787387
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Vascular Biology, Beijing Anzhen Hospital RCV001374824 SCV001439573 likely pathogenic Isolated thoracic aortic aneurysm 2018-09-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV002537626 SCV003442978 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-05-27 criteria provided, single submitter clinical testing Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 c.164G nucleotide in the FBN1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 19293843). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. 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: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 982354). This missense change has been observed in individuals with FBN1-related conditions (PMID: 22772377, 33824467). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 55 of the FBN1 protein (p.Gly55Glu). This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon.

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