Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001880001 | SCV002158041 | uncertain significance | Costello syndrome | 2021-09-28 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 HRAS protein function. ClinVar contains an entry for this variant (Variation ID: 981547). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 125 of the HRAS protein (p.Val125Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. |
Service de Génétique Moléculaire, |
RCV001261052 | SCV001438454 | uncertain significance | Noonan syndrome | no assertion criteria provided | clinical testing |