Submissions for variant NM_005228.5(EGFR):c.2305G>A (p.Val769Met)

gnomAD frequency: 0.00001  dbSNP: rs147149347

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001066254	SCV001231261	uncertain significance	EGFR-related lung cancer	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 769 of the EGFR protein (p.Val769Met). This variant is present in population databases (rs147149347, gnomAD 0.02%). This missense change has been observed in individual(s) with lung cancer (PMID: 32913967). ClinVar contains an entry for this variant (Variation ID: 208821). 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 EGFR protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on EGFR function (PMID: 32913967). 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.
Sema4, Sema4	RCV002257485	SCV002537346	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-26	criteria provided, single submitter	curation
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000206947	SCV000244013	uncertain significance	Lung carcinoma	2013-06-27	no assertion criteria provided	literature only