Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_001369786.1 | Alternative | 5417 nt | 178–747 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
OpenThis sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 65 of the KRAS protein (p.Ser65Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of KRAS-related conditions (PMID: 25326635, 26822237). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 438796). 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. For these reasons, this variant has been classified as Pathogenic.
"This variant has been reported in ClinVar as Uncertain significance (1 clinical laboratories) and as Pathogenic (1 clinical laboratories) and as Likely pathogenic by ClinGen RASopathy Variant Curation Expert Panel expert panel."
COSMIC Somatic Evidence
Open
Functional Impact & Domains
Functional Domain
Error in OpenAI Consolidation. OncoKB: KRASS65IKRASS65ISomaticNCBI Gene:3845|Show additional gene information Variant OverviewKRAS, a GTPase which functions as an upstream regulator of the MAPK pathway, is frequently mutated in various cancer types including lung, colorectal and pancreatic cancers.The KRAS S65I mutation has not specifically been reviewed by the OncoKB team. However, KRAS S65N is known to be oncogenic, and therefore KRAS S65I is considered likely oncogenic.Hide mutation effect description The KRAS S65I mutation has not specifically been reviewed by the OncoKB team. However, the mutation effect description for KRAS S65N, an alternate allele of KRAS S65I, is: The KRAS S65N mutation is located in the Switch II region of the catalytic G-domain of the protein. This mutation has been found in thyroid cancer (PMID: 24798740). Expression of this mutation in human embryonic kidney and thyroid cancer cells demonstrated that it is activating, as measured by increased pathway activation and cell proliferation compared to wildtype (PMID: 8626650, 24798740). JAX-CKB: No results found
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Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.0 | None bp |
| Donor Loss (DL) | 0.0 | None bp |
| Acceptor Gain (AG) | 0.0 | None bp |
| Donor Gain (DG) | 0.0 | None bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PS3 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)
PM2 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)
PP5 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)