Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001328521 | SCV000623397 | uncertain significance | Renal cell carcinoma | 2023-09-08 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with an unspecified cancer (PMID: 28873162). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 663 of the MET protein (p.Ser663Leu). This variant is present in population databases (rs376459715, gnomAD 0.008%). ClinVar contains an entry for this variant (Variation ID: 454204). 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. |
Eurofins Ntd Llc |
RCV000592240 | SCV000706958 | uncertain significance | not provided | 2017-03-31 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000532305 | SCV000838258 | uncertain significance | Papillary renal cell carcinoma type 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001013919 | SCV001174563 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-21 | criteria provided, single submitter | clinical testing | The p.S663L variant (also known as c.1988C>T), located in coding exon 7 of the MET gene, results from a C to T substitution at nucleotide position 1988. The serine at codon 663 is replaced by leucine, an amino acid with dissimilar properties. This alteration was detected in a cohort of 1663 Brazilian breast cancer patients who underwent hereditary multigene panel testing (Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). 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 this alteration remains unclear. |
Sema4, |
RCV001013919 | SCV002532114 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-13 | criteria provided, single submitter | curation | |
Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003153672 | SCV003843360 | benign | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003459163 | SCV004192509 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-09-11 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000592240 | SCV005078947 | uncertain significance | not provided | 2023-12-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25759019, 27997549, 28873162, 35264596) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000592240 | SCV005622896 | uncertain significance | not provided | 2023-11-17 | criteria provided, single submitter | clinical testing |