Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000335138 | SCV000466439 | uncertain significance | Papillary renal cell carcinoma type 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Ambry Genetics | RCV000570504 | SCV000673777 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-05 | criteria provided, single submitter | clinical testing | The p.P392T variant (also known as c.1174C>A), located in coding exon 1 of the MET gene, results from a C to A substitution at nucleotide position 1174. The proline at codon 392 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is not 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. |
Fulgent Genetics, |
RCV000765918 | SCV000897338 | uncertain significance | Osteofibrous dysplasia; Papillary renal cell carcinoma type 1; Hepatocellular carcinoma; Autosomal recessive nonsyndromic hearing loss 97 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001312205 | SCV001411807 | uncertain significance | Renal cell carcinoma | 2023-02-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 392 of the MET protein (p.Pro392Thr). This variant is not present in population databases (gnomAD no frequency). 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: 358684). 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. |
Center for Genomic Medicine, |
RCV003320637 | SCV004025159 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003470320 | SCV004192488 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-10-03 | criteria provided, single submitter | clinical testing |