ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.5087A>G (p.Tyr1696Cys)

dbSNP: rs387906625
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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 RCV001262145 SCV001439911 uncertain significance Marfan syndrome 2019-01-01 criteria provided, single submitter clinical testing
Invitae RCV003764623 SCV004571017 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-07-03 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1696 of the FBN1 protein (p.Tyr1696Cys). For these reasons, this variant has been classified as Pathogenic. 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: 29699). This missense change has been observed in individual(s) with autosomal dominant geleophysic dysplasia (PMID: 21683322, 33082559). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency).
Human Genetics Section, Sidra Medicine RCV000022548 SCV004708153 likely pathogenic Geleophysic dysplasia 2 2024-02-28 criteria provided, single submitter research The missense variant is located in a mutational hot spot and missense variants are a common mechanism of disease. The variant is denovo. The same codon with a different amino acid change was found as a known pathogenic. ClinVar contains an entry for this variant (Variation ID: 29699). The variant is low in frequency in population databases (no frequency in GnomAD). We thus classify the variant as likely pathogenic
OMIM RCV000022548 SCV000043837 pathogenic Geleophysic dysplasia 2 2018-01-04 no assertion criteria provided literature only

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