ClinVar Miner

Submissions for variant NM_000245.4(MET):c.34C>T (p.Leu12Phe)

gnomAD frequency: 0.00002  dbSNP: rs764455004
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001947130 SCV002132298 likely benign Renal cell carcinoma 2023-11-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002334765 SCV002618686 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-01 criteria provided, single submitter clinical testing The p.L12F variant (also known as c.34C>T), located in coding exon 1 of the MET gene, results from a C to T substitution at nucleotide position 34. The leucine at codon 12 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). 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.
GeneDx RCV004762209 SCV005368934 uncertain significance not provided 2023-06-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed among control individuals, but absent from cases, in a melanoma case-control study (Pritchard et al., 2018); This variant is associated with the following publications: (PMID: 29641532)

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