ClinVar Miner

Submissions for variant NM_005228.5(EGFR):c.2180A>G (p.Tyr727Cys)

gnomAD frequency: 0.00007  dbSNP: rs138240620
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001326568 SCV001517605 uncertain significance EGFR-related lung cancer 2024-12-23 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 727 of the EGFR protein (p.Tyr727Cys). This variant is present in population databases (rs138240620, 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: 1026153). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Sema4, Sema4 RCV002258203 SCV002537340 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-22 criteria provided, single submitter curation
Ambry Genetics RCV002258203 SCV005579633 likely benign Hereditary cancer-predisposing syndrome 2024-10-28 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 RCV005038080 SCV005668419 uncertain significance Inflammatory skin and bowel disease, neonatal, 2; Lung cancer 2024-05-06 criteria provided, single submitter clinical testing

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