Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000635696 | SCV000757117 | uncertain significance | Familial cancer of breast | 2018-11-21 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This variant has been observed in an individual undergoing Lynch syndrome genetic testing (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 530076). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with phenylalanine at codon 285 of the CHEK2 protein (p.Ile285Phe). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and phenylalanine. |