Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000197316 | SCV000250279 | uncertain significance | not provided | 2018-12-04 | criteria provided, single submitter | clinical testing | The E1036K variant of uncertain significance in the FBN2 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). E1036K is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, The E1036K variant 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 congenital contractural arachnodactyly (Collod-Beroud et al., 2003; Frédéric et al., 2009).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. |
Blueprint Genetics | RCV000197316 | SCV000927762 | uncertain significance | not provided | 2018-06-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003525879 | SCV004329727 | likely benign | Congenital contractural arachnodactyly | 2024-01-26 | criteria provided, single submitter | clinical testing |