ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.3338A>G (p.Asp1113Gly)

dbSNP: rs140597
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000802396 SCV000942226 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-05-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects FBN1 function (PMID: 17324963). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 549158). This missense change has been observed in individuals with clinical features of Marfan syndrome and Marfan syndrome (PMID: 10464652, 17663468, 28941062; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1113 of the FBN1 protein (p.Asp1113Gly).
Centre of Medical Genetics, University of Antwerp RCV000663632 SCV002025575 likely pathogenic Marfan syndrome 2021-03-01 criteria provided, single submitter research PM2, PS6, PP4
GeneDx RCV002284420 SCV002574208 likely pathogenic not provided 2022-08-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Published in vitro functional studies show processing and secretion from fibroblasts as well as incorporation into micofibrils similar to wild type protein (Jensen et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11875032, 10464652, 17663468, 17253931, 28941062, 31825148, 20591885, 18852891, 18974781, 26659599, 24941995, 20886638, 33735269)
Center for Medical Genetics Ghent, University of Ghent RCV000663632 SCV000786954 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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