Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000480896 | SCV000343038 | uncertain significance | not provided | 2018-03-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000480896 | SCV000571198 | likely pathogenic | not provided | 2016-08-10 | criteria provided, single submitter | clinical testing | The R522C variant in the FGD1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R522C variant 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. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variants in the same amino acid residue (R522H) has been reported in one family with Aarskog-Scott syndrome (Schwartz et al., 2000), supporting the functional importance of this region of the protein. The R522C variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |