Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
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, |
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, |
RCV005036310 | SCV005668416 | uncertain significance | Inflammatory skin and bowel disease, neonatal, 2; Lung cancer | 2024-01-24 | criteria provided, single submitter | clinical testing |