Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000219618 | SCV000275085 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-07 | criteria provided, single submitter | clinical testing | The p.T387N variant (also known as c.1160C>A), located in coding exon 10 of the CHEK2 gene, results from a C to A substitution at nucleotide position 1160. The threonine at codon 387 is replaced by asparagine, an amino acid with similar properties. The Thr-387 residue is an autophosphorylation site located within the activation loop of the Chk2 kinase domain, and has been demonstrated to have a dependency on Chk2 kinase activity for phosphorylation (Wu X et al. Hum. Mutat. 2006 Aug;27(8):742-7; Schwarz JK et al. Mol. Cancer Res. 2003 Jun; 1(8):598-609). 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. |
Invitae | RCV000230901 | SCV000289648 | uncertain significance | Familial cancer of breast | 2023-08-25 | 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: 231287). This missense change has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 21348412). This variant is present in population databases (rs587780168, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 387 of the CHEK2 protein (p.Thr387Asn). |
Color Diagnostics, |
RCV000219618 | SCV000689634 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-17 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001818527 | SCV002064598 | uncertain significance | not specified | 2019-06-25 | criteria provided, single submitter | clinical testing |