ClinVar Miner

Submissions for variant NM_000245.4(MET):c.3218C>T (p.Pro1073Leu)

gnomAD frequency: 0.00007  dbSNP: rs370529693
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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 RCV001312227 SCV000166423 uncertain significance Renal cell carcinoma 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1091 of the MET protein (p.Pro1091Leu). This variant is present in population databases (rs370529693, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 135966). 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 not expected to disrupt MET protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000164064 SCV000214674 likely benign Hereditary cancer-predisposing syndrome 2019-03-07 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics RCV003492548 SCV000838270 likely benign Hereditary cancer 2024-01-23 criteria provided, single submitter clinical testing
GeneDx RCV001534185 SCV001751089 uncertain significance not provided 2024-06-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast and colon cancer (PMID: 29684080, 35264596); This variant is associated with the following publications: (PMID: 35210353, 35264596, 29684080)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002228447 SCV002511600 likely benign not specified 2022-04-08 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001534185 SCV003808792 uncertain significance not provided 2019-05-10 criteria provided, single submitter clinical testing

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