Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002004727 | SCV002232381 | uncertain significance | Renal cell carcinoma | 2023-03-13 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.003%). 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MET protein function. ClinVar contains an entry for this variant (Variation ID: 1449962). This variant has not been reported in the literature in individuals affected with MET-related conditions. This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 596 of the MET protein (p.Phe596Tyr). |
Ambry Genetics | RCV002407169 | SCV002717169 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-08-31 | criteria provided, single submitter | clinical testing | The p.F596Y variant (also known as c.1787T>A), located in coding exon 5 of the MET gene, results from a T to A substitution at nucleotide position 1787. The phenylalanine at codon 596 is replaced by tyrosine, an amino acid with highly similar properties. 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 5911 samples (11822 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. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.F596Y remains unclear. |