Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001020289 | SCV001181745 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-08 | criteria provided, single submitter | clinical testing | The p.W114C variant (also known as c.342G>T), located in coding exon 2 of the CHEK2 gene, results from a G to T substitution at nucleotide position 342. The tryptophan at codon 114 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well 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. |
Invitae | RCV001050856 | SCV001214985 | uncertain significance | Familial cancer of breast | 2022-08-16 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 823764). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (rs756949505, gnomAD 0.003%). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 114 of the CHEK2 protein (p.Trp114Cys). |
Color Diagnostics, |
RCV001020289 | SCV001358493 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-04-06 | criteria provided, single submitter | clinical testing | This missense variant replaces tryptophan with cysteine at codon 114 of the CHEK2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251202 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Sema4, |
RCV001020289 | SCV002537423 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-10 | criteria provided, single submitter | curation | |
MGZ Medical Genetics Center | RCV001050856 | SCV002579320 | uncertain significance | Familial cancer of breast | 2021-07-09 | criteria provided, single submitter | clinical testing |