Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001052646 | SCV001216867 | uncertain significance | Renal cell carcinoma | 2023-08-30 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 41621). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is present in population databases (rs202047059, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 67 of the MET protein (p.Thr67Ala). |
Ambry Genetics | RCV002415458 | SCV002721782 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-09 | criteria provided, single submitter | clinical testing | The p.T67A variant (also known as c.199A>G), located in coding exon 1 of the MET gene, results from an A to G substitution at nucleotide position 199. The threonine at codon 67 is replaced by alanine, an amino acid with similar properties. This variant was detected as a secondary finding in 1 out of 572 ClinSeq participants, unselected for personal or family history of cancer, who underwent exome sequencing; however, the clinical information for this particular individual was not provided (Johnston JJ et al. Am J Hum Genet, 2012 Jul;91:97-108). This amino acid position is poorly 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. |
Gene |
RCV000034526 | SCV005419436 | uncertain significance | not provided | 2024-05-28 | 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; Observed in an individual with atherosclerosis (PMID: 22703879); This variant is associated with the following publications: (PMID: 22703879) |
Biesecker Lab/Clinical Genomics Section, |
RCV000034526 | SCV000043292 | variant of unknown significance | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Uncertain significance. |