Submissions for variant NM_000245.4(MET):c.1306G>C (p.Glu436Gln)

dbSNP: rs200740468

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001174618	SCV001337822	uncertain significance	not specified	2020-01-17	criteria provided, single submitter	clinical testing	Variant summary: MET c.1306G>C (p.Glu436Gln) results in a conservative amino acid change located in the Sema domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 249442 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1306G>C has not been reported in the literature in individuals affected with Papillary Renal Cell Carcinoma. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003764657	SCV004632061	uncertain significance	Renal cell carcinoma	2022-11-04	criteria provided, single submitter	clinical testing	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. 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. ClinVar contains an entry for this variant (Variation ID: 41617). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 436 of the MET protein (p.Glu436Gln).
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034522	SCV000043305	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.