Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001020069 | SCV001181500 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-20 | criteria provided, single submitter | clinical testing | The c.3355G>A (p.D1119N) alteration is located in exon 16 (coding exon 15) of the MET gene. This alteration results from a G to A substitution at nucleotide position 3355, causing the aspartic acid (D) at amino acid position 1119 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV001860970 | SCV002172334 | uncertain significance | Renal cell carcinoma | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1119 of the MET protein (p.Asp1119Asn). This variant is present in population databases (rs749678495, gnomAD 0.0009%). 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: 823653). 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. |
Gene |
RCV003235448 | SCV003933327 | uncertain significance | not provided | 2024-06-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |