Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001044048 | SCV001207822 | uncertain significance | EGFR-related lung cancer | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 165 of the EGFR protein (p.Arg165Trp). This variant is present in population databases (rs587778252, gnomAD 0.009%). 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: 134032). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Genetic Services Laboratory, |
RCV000120701 | SCV002069406 | uncertain significance | not specified | 2021-05-14 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the EGFR gene demonstrated a sequence change, c.493C>T, in exon 4 that results in an amino acid change, p.Arg165Trp. This sequence change does not appear to have been previously described in individuals with EGFR-related disorders. This sequence change has been described in the gnomAD database with a low frequency of 0.009% in the non-Finnish European subpopulation (dbSNP rs587778252). The p.Arg165Trp change affects a poorly conserved amino acid residue located in a domain of the EGFR protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg165Trp substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Arg165Trp change remains unknown at this time. |
ITMI | RCV000120701 | SCV000084862 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |