ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1988C>T (p.Ser663Leu)

gnomAD frequency: 0.00005  dbSNP: rs376459715
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp 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 (ga) 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, Sema4 RCV001013919 SCV002532114 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-13 criteria provided, single submitter curation
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University 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
GeneDx 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

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