ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.4313G>A (p.Ser1438Asn) (rs587782945)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000143892 SCV000188761 uncertain significance Marfan syndrome 2014-01-29 no assertion criteria provided clinical testing
GeneDx RCV000181517 SCV000233820 uncertain significance not provided 2014-03-15 criteria provided, single submitter clinical testing p.Ser1438Asn (AGT>AAT): c.4313 G>A (NM_000138.4) The S1438N variant has not been published as a mutation or as a benign polymorphism to our knowledge. No population data is available for this substitution. The S1438N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species within the calcium binding domain. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense mutations in nearby residues (C1431W, C1431Y, C1429S, Y1427C, Y1427D) have been reported in association with Marfan syndrome, supporting the functional importance of this region of the protein, however most of them involve a Cysteine substitution.Therefore, based on the currently available information, it is unclear whether these variants are pathogenic mutations or a rare benign variants. The variant is found in TAAD panel(s).
Illumina Clinical Services Laboratory,Illumina RCV000381005 SCV000392354 uncertain significance Geleophysic dysplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000291329 SCV000392355 uncertain significance Acromicric dysplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000346355 SCV000392356 uncertain significance Ectopia lentis 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000405079 SCV000392357 uncertain significance Stiff skin syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000302074 SCV000392358 uncertain significance Thoracic aortic aneurysm and aortic dissection 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000143892 SCV000392359 uncertain significance Marfan syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000397810 SCV000392360 uncertain significance MASS syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000298555 SCV000392361 uncertain significance Weill-Marchesani syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000818523 SCV000959142 uncertain significance Marfan syndrome; Thoracic aortic aneurysm and aortic dissection 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 1438 of the FBN1 protein (p.Ser1438Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs587782945, ExAC 0.08%). This variant has been reported in the literature in an individual with suspected FBN1-related disease (PMID: 27906200). ClinVar contains an entry for this variant (Variation ID: 155792). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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