Submissions for variant NM_005228.5(EGFR):c.769G>A (p.Glu257Lys)

gnomAD frequency: 0.00035  dbSNP: rs138847501

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001453910	SCV001657620	likely benign	EGFR-related lung cancer	2025-01-27	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002258268	SCV002537715	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-18	criteria provided, single submitter	curation
Revvity Omics, Revvity	RCV003145666	SCV003831835	uncertain significance	not provided	2019-09-03	criteria provided, single submitter	clinical testing
GeneDx	RCV003145666	SCV004034857	uncertain significance	not provided	2023-03-06	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Observed in individuals with breast cancer, clear cell renal carcinoma, and/or cervical cancer (Huang et al., 2018); Observed in the germline of a child with an adrenocortical tumor; however, the child had a presumptive diagnosis of Beckwith-Wiedemann syndrome (BWS) (Pinto et al., 2021); This variant is associated with the following publications: (PMID: 36561320, 29625052, 34803919)
Ambry Genetics	RCV002258268	SCV005579582	benign	Hereditary cancer-predisposing syndrome	2024-08-23	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV005038228	SCV005668396	uncertain significance	Inflammatory skin and bowel disease, neonatal, 2; Lung cancer	2024-01-19	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003965895	SCV004785603	likely benign	EGFR-related disorder	2024-02-14	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).