ClinVar Miner

Submissions for variant NM_005228.5(EGFR):c.1367T>C (p.Ile456Thr)

dbSNP: rs1177337471
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001774990 SCV002004327 uncertain significance not provided 2019-12-18 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001885091 SCV002174427 uncertain significance EGFR-related lung cancer 2023-04-08 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 456 of the EGFR protein (p.Ile456Thr). This variant is not present in population databases (gnomAD no frequency). 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: 1316618). 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 expected to disrupt EGFR protein function. 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.
Ambry Genetics RCV005330905 SCV005997975 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-19 criteria provided, single submitter clinical testing The p.I456T variant (also known as c.1367T>C), located in coding exon 12 of the EGFR gene, results from a T to C substitution at nucleotide position 1367. The isoleucine at codon 456 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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