Submissions for variant NM_005228.5(EGFR):c.3368C>T (p.Pro1123Leu)

gnomAD frequency: 0.00001  dbSNP: rs775317295

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001364941	SCV001561148	uncertain significance	EGFR-related lung cancer	2024-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1123 of the EGFR protein (p.Pro1123Leu). This variant is present in population databases (rs775317295, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with EGFR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1056156). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
PreventionGenetics, part of Exact Sciences	RCV004753298	SCV005346692	uncertain significance	EGFR-related disorder	2024-09-08	no assertion criteria provided	clinical testing	The EGFR c.3368C>T variant is predicted to result in the amino acid substitution p.Pro1123Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0027% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1056156/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.