Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000696560 | SCV000825124 | uncertain significance | Familial cancer of breast | 2023-09-26 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 574591). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 438 of the CHEK2 protein (p.Asp438Gly). |
Color Diagnostics, |
RCV001176908 | SCV001341008 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-18 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 438 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hereditary nonpolyposis colorectal cancer (PMID: 31942411). This variant has not been identified 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. |
Gene |
RCV002469266 | SCV002765194 | uncertain significance | not provided | 2022-12-13 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in an individual with colorectal cancer (Staninova-Stojovska et al., 2019); Published functional studies demonstrate DNA damage response comparable to wild-type in a yeast-based assay (Delimitsou et al., 2019; This variant is associated with the following publications: (PMID: 19782031, 22419737, 31942411, 30851065) |