Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001878806 | SCV002130174 | uncertain significance | RASopathy | 2021-04-29 | 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 SOS1 protein function. This variant has not been reported in the literature in individuals with SOS1-related conditions. This variant is present in population databases (rs768975865, ExAC 0.009%). This sequence change replaces cysteine with tyrosine at codon 167 of the SOS1 protein (p.Cys167Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. |