ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1315C>T (p.Gln439Ter)

dbSNP: rs778989252
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217777 SCV000273665 pathogenic Hereditary cancer-predisposing syndrome 2023-10-09 criteria provided, single submitter clinical testing The p.Q439* pathogenic mutation (also known as c.1315C>T), located in coding exon 11 of the CHEK2 gene, results from a C to T substitution at nucleotide position 1315. This changes the amino acid from a glutamine to a stop codon within coding exon 11. This alteration has been reported in at least one subject in a study of 13087 breast cancer cases and 5488 control individuals in the UK (Decker B et al. J. Med. Genet., 2017 11;54:732-741). This alteration has also been reported in one patient from a cohort of 618 unselected Chinese colorectal cancer patients (Gong R et al. Cancer Manag Res, 2019 Apr;11:3721-3739). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
GeneDx RCV000255686 SCV000322548 pathogenic not provided 2023-08-29 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with personal or family history of breast or colorectal cancer (Decker et al., 2017; Dong et al., 2018; Gong et al., 2019); This variant is associated with the following publications: (PMID: 32805687, 28779002, 30039884, 31118792, Sadaps2019[Abstract])
Counsyl RCV000576345 SCV000677836 likely pathogenic Familial cancer of breast 2017-04-20 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000217777 SCV000689648 pathogenic Hereditary cancer-predisposing syndrome 2022-09-16 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 12 of the CHEK2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed in two individuals affected with breast cancer and two unaffected individuals in breast cancer case-control studies (PMID: 28779002, 33471991). It has also been reported in an individual with colorectal cancer (PMID: 31118792). This variant has been identified in 1/251024 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of CHEK2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000576345 SCV000815239 pathogenic Familial cancer of breast 2024-11-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln439*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 230206). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (internal data). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000255686 SCV002019279 pathogenic not provided 2019-02-01 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000576345 SCV004020124 pathogenic Familial cancer of breast 2023-03-08 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Baylor Genetics RCV000576345 SCV004217708 pathogenic Familial cancer of breast 2023-12-27 criteria provided, single submitter clinical testing

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