ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1232G>A (p.Trp411Ter) (rs371418985)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000448496 SCV000581179 pathogenic Hereditary cancer-predisposing syndrome 2018-02-02 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 RCV000448496 SCV000537650 pathogenic Hereditary cancer-predisposing syndrome 2016-08-29 criteria provided, single submitter clinical testing
Counsyl RCV000465371 SCV000677827 likely pathogenic Familial cancer of breast 2017-04-18 criteria provided, single submitter clinical testing
GeneDx RCV000220219 SCV000279396 likely pathogenic not provided 2016-11-14 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.1232G>A at the cDNA level and p.Trp411Ter (W411X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered likely pathogenic.
GeneKor MSA RCV000448496 SCV000821723 likely pathogenic Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000465371 SCV000550559 pathogenic Familial cancer of breast 2018-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp411*) 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 not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 234505). Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.

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