ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.2207A>G (p.Asn736Ser)

dbSNP: rs1566912242
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001706705 SCV001934338 likely benign Marfan syndrome 2020-11-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002533776 SCV003482215 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-09-29 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: 617875). This missense change has been observed in individual(s) with clinical features of FBN1-related conditions (PMID: 26621581). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 736 of the FBN1 protein (p.Asn736Ser).
All of Us Research Program, National Institutes of Health RCV001706705 SCV004829395 uncertain significance Marfan syndrome 2023-05-16 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 736 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in a family affected with thoracic aortic aneurysms and dissections but the variant was reported to not segregate with disease in the family (PMID: 26621581). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
University of Washington Center for Mendelian Genomics, University of Washington RCV000755200 SCV000883029 likely benign Congenital aneurysm of ascending aorta; Acute aortic dissection 2016-01-20 no assertion criteria provided research

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