Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001861474 | SCV002285672 | likely pathogenic | RASopathy | 2022-08-16 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ala146 amino acid residue in KRAS. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 KRAS protein function. ClinVar contains an entry for this variant (Variation ID: 375963). This variant has not been reported in the literature as a germline variant in individuals affected with KRAS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 146 of the KRAS protein (p.Ala146Pro). |
Kasturba Medical College, |
RCV002259922 | SCV002540116 | pathogenic | Autoimmune lymphoproliferative syndrome type 4 | criteria provided, single submitter | clinical testing | ||
Database of Curated Mutations |
RCV000444020 | SCV000504417 | pathogenic | Neoplasm of the large intestine | 2014-10-02 | no assertion criteria provided | literature only | |
Xiao lab, |
RCV000984134 | SCV001132105 | likely pathogenic | Multiple myeloma | 2019-08-31 | no assertion criteria provided | clinical testing |