ClinVar Miner

Submissions for variant NM_004985.5(KRAS):c.437C>T (p.Ala146Val)

gnomAD frequency: 0.00001  dbSNP: rs1057519725
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002524688 SCV002960445 pathogenic RASopathy 2022-07-25 criteria provided, single submitter clinical testing 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. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 146 of the KRAS protein (p.Ala146Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with mosaic RASopathy (PMID: 26970110, 30891959). ClinVar contains an entry for this variant (Variation ID: 375962). Experimental studies have shown that this missense change affects KRAS function (PMID: 30448735). 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. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn RCV003488585 SCV004239231 uncertain significance not provided 2023-11-14 criteria provided, single submitter clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV004760489 SCV005373897 likely pathogenic Familial pancreatic carcinoma 2024-09-22 criteria provided, single submitter clinical testing
OMIM RCV000791299 SCV000930609 pathogenic OCULOECTODERMAL SYNDROME, SOMATIC 2022-03-09 no assertion criteria provided literature only
GeneReviews RCV001839452 SCV002099551 not provided Encephalocraniocutaneous lipomatosis no assertion provided literature only
Laboratory of Urology, Hospital Clinic de Barcelona RCV003332167 SCV004040498 pathogenic Malignant tumor of urinary bladder no assertion criteria provided research

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