ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.3931T>A (p.Tyr1311Asn)

gnomAD frequency: 0.00001  dbSNP: rs1406315227
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001258188 SCV001435077 uncertain significance Marfan syndrome criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV002223293 SCV002501289 uncertain significance not provided 2022-02-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002486004 SCV002788602 uncertain significance Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome 2021-10-16 criteria provided, single submitter clinical testing
Invitae RCV002570635 SCV003446477 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1311 of the FBN1 protein (p.Tyr1311Asn). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of Marfan syndrome (PMID: 25652356). ClinVar contains an entry for this variant (Variation ID: 979123). 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 with a positive predictive value of 95%. This variant disrupts the p.Tyr1311 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27906200, 31131229). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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