ClinVar Miner

Submissions for variant NM_000245.4(MET):c.305G>A (p.Ser102Asn)

gnomAD frequency: 0.00001  dbSNP: rs779897466
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV003492138 SCV000838232 likely benign Hereditary cancer 2024-01-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001358795 SCV000952738 uncertain significance Renal cell carcinoma 2023-08-27 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MET-related conditions. This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 102 of the MET protein (p.Ser102Asn). This variant is present in population databases (rs779897466, gnomAD 0.003%). ClinVar contains an entry for this variant (Variation ID: 584707). 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.
Ambry Genetics RCV004026760 SCV005037949 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-17 criteria provided, single submitter clinical testing The p.S102N variant (also known as c.305G>A), located in coding exon 1 of the MET gene, results from a G to A substitution at nucleotide position 305. The serine at codon 102 is replaced by asparagine, an amino acid with highly similar 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 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.

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