ClinVar Miner

Submissions for variant NM_005228.5(EGFR):c.2963A>G (p.His988Arg)

dbSNP: rs17290699
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001071864 SCV001237194 uncertain significance EGFR-related lung cancer 2025-01-13 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 988 of the EGFR protein (p.His988Arg). This variant is present in population databases (rs17290699, gnomAD 0.005%). 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: 864633). 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003238302 SCV002009725 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV005328531 SCV005998007 uncertain significance Hereditary cancer-predisposing syndrome 2025-01-16 criteria provided, single submitter clinical testing The p.H988R variant (also known as c.2963A>G), located in coding exon 25 of the EGFR gene, results from an A to G substitution at nucleotide position 2963. The histidine at codon 988 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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