Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000235978 | SCV000294277 | uncertain significance | Renal cell carcinoma | 2023-05-23 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 246639). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1166*) in the MET gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MET cause disease. |
| Ambry Genetics | RCV002450740 | SCV002617247 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-08-31 | criteria provided, single submitter | clinical testing | The p.R1166* variant (also known as c.3496C>T), located in coding exon 16 of the MET gene, results from a C to T substitution at nucleotide position 3496. This changes the amino acid from an arginine to a stop codon within coding exon 16. While premature stop codons are typically deleterious in nature for tumor suppressor genes, the MET gene is a well described proto-oncogene and the cancer related phenotype is conventionally due to activating mutations. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6050 samples (12100 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.02% (greater than 4500 alleles tested) in our clinical cohort. Since supporting evidence is limited at this time, the clinical significance of p.R1166* remains unclear. |