ClinVar Miner

Submissions for variant NM_004985.5(KRAS):c.436G>A (p.Ala146Thr)

dbSNP: rs121913527
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178223 SCV000230243 uncertain significance not provided 2014-06-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852208 SCV002282857 likely pathogenic RASopathy 2021-12-16 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects KRAS function (PMID: 20147967, 20570890, 26110767). 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: 197243). This variant has not been reported in the literature 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 threonine, which is neutral and polar, at codon 146 of the KRAS protein (p.Ala146Thr).
Pathology Department, Puerta del Mar University Hospital RCV002227934 SCV002507273 uncertain significance Classic Hodgkin lymphoma 2021-10-01 criteria provided, single submitter research
CeGaT Center for Human Genetics Tuebingen RCV000178223 SCV003917190 pathogenic not provided 2023-01-01 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV004554743 SCV005044043 pathogenic Cardiofaciocutaneous syndrome 2 2024-01-30 criteria provided, single submitter clinical testing PS3, SP4, PM1
Database of Curated Mutations (DoCM) RCV000426420 SCV000504418 pathogenic Neoplasm of the large intestine 2015-07-14 no assertion criteria provided literature only
OMIM RCV000791298 SCV000930608 pathogenic OCULOECTODERMAL SYNDROME, SOMATIC 2022-03-09 no assertion criteria provided literature only
GeneReviews RCV001839448 SCV002099550 not provided Encephalocraniocutaneous lipomatosis no assertion provided literature only

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