ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1168T>A (p.Tyr390Asn)

dbSNP: rs2052558996
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001232222 SCV001404770 uncertain significance Familial cancer of breast 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 390 of the CHEK2 protein (p.Tyr390Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 958958). 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. This variant disrupts the p.Tyr390 amino acid residue in CHEK2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22114986, 25503501, 27553368, 27751358, 30441849, 30613976, 30851065, 32957588, 33919281, 33925588, 34903604, 35220195; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Ambry Genetics RCV002327556 SCV002630751 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-31 criteria provided, single submitter clinical testing The p.Y390N variant (also known as c.1168T>A), located in coding exon 10 of the CHEK2 gene, results from a T to A substitution at nucleotide position 1168. The tyrosine at codon 390 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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