Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000440752 | SCV000535034 | uncertain significance | not provided | 2019-04-24 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); Identified in conjunction with additional variants in individuals referred for connective tissue disorder genetic testing at GeneDx; segregation data is absent at this time; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; In-silico splicing algorithms suggest this variant results in the creation of a cryptic splice donor site; in the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Does not affect a cysteine residue within a calcium-binding EGF-like domain of the FBN2 gene; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN2-related disorders (Collod-Beroud et al., 2003; Frederic et al., 2009) |