Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001016779 | SCV001177775 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-05 | criteria provided, single submitter | clinical testing | The p.T950I variant (also known as c.2849C>T), located in coding exon 12 of the MET gene, results from a C to T substitution at nucleotide position 2849. The threonine at codon 950 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV001068809 | SCV001233941 | uncertain significance | Renal cell carcinoma | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 950 of the MET protein (p.Thr950Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 821897). 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. 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 |
RCV001759698 | SCV002007409 | uncertain significance | not provided | 2023-02-16 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Baylor Genetics | RCV004569955 | SCV005057887 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-12-27 | criteria provided, single submitter | clinical testing |