Submissions for variant NM_005228.5(EGFR):c.1570G>A (p.Val524Ile)

gnomAD frequency: 0.00001  dbSNP: rs587778249

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001226299	SCV001398610	uncertain significance	EGFR-related lung cancer	2023-11-29	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 524 of the EGFR protein (p.Val524Ile). This variant is present in population databases (rs587778249, gnomAD 0.009%). 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: 134022). 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%. 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.
Mendelics	RCV000120691	SCV002519152	benign	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153387	SCV003843535	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV004791271	SCV005409257	uncertain significance	not provided	2024-03-27	criteria provided, single submitter	clinical testing	BP4
ITMI	RCV000120691	SCV000084852	not provided	not specified	2013-09-19	no assertion provided	reference population