Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000309625 | SCV000329747 | pathogenic | not provided | 2016-03-30 | criteria provided, single submitter | clinical testing | The R610Q pathogenic variant in the FGD1 gene has been reported previously in association with Aarskog-Scott syndrome (Orrico et al., 2000). Functional studies demonstrate that the R610Q variant results in aberrant FGD1 activity (Zou et al., 2011). 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 R610Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some 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. We interpret R610Q as a pathogenic variant. |
Invitae | RCV000309625 | SCV003445242 | pathogenic | not provided | 2022-06-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 10825). This missense change has been observed in individuals with Aarskog-Scott syndrome (PMID: 10930571; 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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 610 of the FGD1 protein (p.Arg610Gln). 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 FGD1 protein function. |
OMIM | RCV000011572 | SCV000031804 | pathogenic | Aarskog syndrome | 2000-08-04 | no assertion criteria provided | literature only |