ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.591del (p.Val198fs) (rs587782245)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130949 SCV000185863 pathogenic Hereditary cancer-predisposing syndrome 2018-03-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000130949 SCV000684664 pathogenic Hereditary cancer-predisposing syndrome 2015-03-05 criteria provided, single submitter clinical testing
Counsyl RCV000204563 SCV000488810 likely pathogenic Familial cancer of breast 2016-07-05 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000235159 SCV000860260 pathogenic not provided 2018-04-05 criteria provided, single submitter clinical testing
GeneDx RCV000235159 SCV000211013 pathogenic not provided 2018-09-04 criteria provided, single submitter clinical testing This deletion of one nucleotide in CHEK2 is denoted c.591delA at the cDNA level and p.Val198PhefsX7 (V198FfsX7) at the protein level. The normal sequence, with the base that is deleted in brackets, is ATAA[delA]Ggta, where the capital letters are exonic and lowercase are intronic. The deletion causes a frameshift which changes a Valine to a Phenylalanine at codon 198, and creates a premature stop codon at position 7 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. CHEK2 c.591delA, published as 589delA using alternate nomenclature, has been observed in individuals with prostate cancer as well as early-onset or male breast cancer (Bell 2007, Pritchard 2016, Pritzlaff 2017). We consider this variant to be pathogenic.
Invitae RCV000204563 SCV000262460 pathogenic Familial cancer of breast 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val198Phefs*7) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in individuals affected with breast cancer (PMID: 17721994, 26681312, 28008555), and an individual with prostate cancer (PMID: 27433846). This variant is also known as 589delA in the literature. ClinVar contains an entry for this variant (Variation ID: 142114). Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235159 SCV000601174 likely pathogenic not provided 2017-06-02 criteria provided, single submitter clinical testing

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