Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000460515 | SCV000550507 | uncertain significance | Familial cancer of breast | 2023-07-20 | 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: 410043). 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 tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 404 of the CHEK2 protein (p.Tyr404Cys). |
Color Diagnostics, |
RCV001186457 | SCV001352868 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-17 | criteria provided, single submitter | clinical testing | This missense variant replaces tyrosine with cysteine at codon 404 of the CHEK2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 36315097). 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. |
Sema4, |
RCV001186457 | SCV002537029 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-27 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV001186457 | SCV002653670 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-28 | criteria provided, single submitter | clinical testing | The p.Y404C variant (also known as c.1211A>G), located in coding exon 10 of the CHEK2 gene, results from an A to G substitution at nucleotide position 1211. The tyrosine at codon 404 is replaced by cysteine, an amino acid with highly dissimilar 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. |
Baylor Genetics | RCV000460515 | SCV004217630 | uncertain significance | Familial cancer of breast | 2023-07-19 | criteria provided, single submitter | clinical testing |