Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000545570 | SCV000628004 | likely pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2018-10-22 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed to be de novo in an individual affected with Marfan syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 457267). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with arginine at codon 2681 of the FBN1 protein (p.Ile2681Arg). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and arginine. |
Centre of Medical Genetics, |
RCV002245997 | SCV002025471 | likely pathogenic | Marfan syndrome | 2021-03-01 | criteria provided, single submitter | research | PM2, PS1, PP3, PP4 |