Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000468070 | SCV000550482 | uncertain significance | Familial cancer of breast | 2020-10-19 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 410027). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 421 of the CHEK2 protein (p.Leu421Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. |
| Ambry Genetics | RCV000575686 | SCV000676004 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-08-03 | criteria provided, single submitter | clinical testing | The p.L421F variant (also known as c.1261C>T), located in coding exon 11 of the CHEK2 gene, results from a C to T substitution at nucleotide position 1261. The leucine at codon 421 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |