ClinVar Miner

Submissions for variant NM_005228.5(EGFR):c.1936A>C (p.Ile646Leu)

gnomAD frequency: 0.00004  dbSNP: rs140516819
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001038476 SCV001201946 uncertain significance EGFR-related lung cancer 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 646 of the EGFR protein (p.Ile646Leu). This variant is present in population databases (rs140516819, gnomAD 0.04%). 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: 837195). 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.
Baylor Genetics RCV001294103 SCV001482916 uncertain significance Lung cancer 2019-07-31 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Breakthrough Genomics, Breakthrough Genomics RCV004693466 SCV005188519 uncertain significance not provided criteria provided, single submitter not provided
Ambry Genetics RCV004950135 SCV005579583 likely benign Hereditary cancer-predisposing syndrome 2024-08-23 criteria provided, single submitter clinical testing This alteration is classified as likely 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 RCV005036310 SCV005668416 uncertain significance Inflammatory skin and bowel disease, neonatal, 2; Lung cancer 2024-01-24 criteria provided, single submitter clinical testing

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