ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.689C>T (p.Ala230Val)

dbSNP: rs730881685
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160427 SCV000210970 uncertain significance not provided 2016-03-14 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.689C>T at the cDNA level, p.Ala230Val (A230V) at the protein level, and results in the change of an Alanine to a Valine (GCC>GTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. CHEK2 Ala230Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Alanine and Valine share similar properties, this is considered a conservative amino acid substitution. CHEK2 Ala230Val occurs at a position that is conserved across species and is located within the protein kinase domain (Desrichard 2011, Roeb 2012). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether CHEK2 Ala230Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV001025772 SCV001188024 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-03 criteria provided, single submitter clinical testing The p.A230V variant (also known as c.689C>T), located in coding exon 5 of the CHEK2 gene, results from a C to T substitution at nucleotide position 689. The alanine at codon 230 is replaced by valine, an amino acid with similar 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.
Invitae RCV001850265 SCV002131621 uncertain significance Familial cancer of breast 2023-09-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 230 of the CHEK2 protein (p.Ala230Val). 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: 182428). 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 tolerated. 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.

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