Submissions for variant NM_005228.5(EGFR):c.3277A>G (p.Ile1093Val)

gnomAD frequency: 0.00001  dbSNP: rs1788062018

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001970377	SCV002256896	uncertain significance	EGFR-related lung cancer	2021-06-20	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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with EGFR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 1093 of the EGFR protein (p.Ile1093Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine.
PreventionGenetics, part of Exact Sciences	RCV003913473	SCV004731933	uncertain significance	EGFR-related disorder	2023-11-07	no assertion criteria provided	clinical testing	The EGFR c.3277A>G variant is predicted to result in the amino acid substitution p.Ile1093Val. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.