Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012780 | SCV001173280 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-28 | criteria provided, single submitter | clinical testing | The c.1702-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 5 of the MET gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to 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 alteration remains unclear. |
| Labcorp Genetics |
RCV001860722 | SCV002224898 | uncertain significance | Renal cell carcinoma | 2023-05-28 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 819866). 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 affects an acceptor splice site in intron 5 of the MET gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MET cause disease. |