Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000657779 | SCV000779532 | uncertain significance | not provided | 2018-04-26 | criteria provided, single submitter | clinical testing | This variant is denoted MET c.3562C>T at the cDNA level and p.Arg1188Ter (R1188X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA). Although this variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay, the mechanism of disease for hereditary papillary renal carcinoma (HPRC) has been shown to be activating rather than loss of function variants in MET (Schmidt 2004). MET Arg1188Ter has not, to our knowledge, been published in the literature as pathogenic or benign. Based on currently available evidence, it is unclear whether this variant is a pathogenic variant or a benign variant. We consider it to be a variant of uncertain significance. |
Labcorp Genetics |
RCV001855359 | SCV002308435 | uncertain significance | Renal cell carcinoma | 2021-11-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1188*) 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. This variant is not present in population databases (gnomAD no frequency). 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: 546023). 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 | RCV003163028 | SCV003855753 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-25 | criteria provided, single submitter | clinical testing | The p.R1188* variant (also known as c.3562C>T), located in coding exon 16 of the MET gene, results from a C to T substitution at nucleotide position 3562. This changes the amino acid from an arginine to a stop codon within coding exon 16. This alteration is expected to result in protein truncation or nonsense-mediated mRNA decay. However, loss of function of MET has not been established as a mechanism of disease. Based on the available evidence, the clinical significance of this variant remains unclear. |