Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
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, |
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 |