Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000631964 | SCV000753067 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-08-30 | criteria provided, single submitter | clinical testing | 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: 527181). This missense change has been observed in individual(s) with Marfan syndrome (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1344 of the FBN1 protein (p.Gly1344Glu). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282272 | SCV001372396 | likely pathogenic | Familial ectopia lentis | 2022-07-11 | criteria provided, single submitter | clinical testing | Variant summary: FBN1 c.4031G>A (p.Gly1344Glu) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251276 control chromosomes (gnomAD). c.4031G>A has been reported in the literature, co-segregating with disease, in multiple members of one family affected with late-onset isolated ectopia lentis and additional manifestations of microspherophakia, secondary glaucoma with minor skeletal involvement (Yang_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |