ClinVar Miner

Submissions for variant NM_033360.4(KRAS):c.436G>C (p.Ala146Pro)

dbSNP: rs121913527
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Total submissions: 4
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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, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV002259922 SCV002540116 pathogenic Autoimmune lymphoproliferative syndrome type 4 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000444020 SCV000504417 pathogenic Neoplasm of the large intestine 2014-10-02 no assertion criteria provided literature only
Xiao lab, Department of Pathology, Memorial Sloan Kettering Cancer Center RCV000984134 SCV001132105 likely pathogenic Multiple myeloma 2019-08-31 no assertion criteria provided clinical testing

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