ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.7765A>G (p.Arg2589Gly)

dbSNP: rs111413134
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817540 SCV000958107 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-03-10 criteria provided, single submitter clinical testing 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FBN1 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 660361). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2589 of the FBN1 protein (p.Arg2589Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of FBN1-related conditions (PMID: 26272055, 31279664; Invitae). It has also been observed to segregate with disease in related individuals.
GeneDx RCV001759592 SCV001987727 uncertain significance not provided 2020-07-16 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26272055, 31279664)
Mayo Clinic Laboratories, Mayo Clinic RCV001759592 SCV004227413 uncertain significance not provided 2023-01-31 criteria provided, single submitter clinical testing PP2, PP4, PM2_supporting, PS4_moderate

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