ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.725C>T (p.Thr242Ile)

dbSNP: rs765136136
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000777672 SCV000913589 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-13 criteria provided, single submitter clinical testing
Invitae RCV001068002 SCV001233089 uncertain significance Familial cancer of breast 2023-05-22 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 631441). This missense change has been observed in individual(s) with borderline ovarian cancer (PMID: 27616075). This variant is present in population databases (rs765136136, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 242 of the CHEK2 protein (p.Thr242Ile).
Sema4, Sema4 RCV000777672 SCV002537634 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-19 criteria provided, single submitter curation
Ambry Genetics RCV000777672 SCV002672492 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-25 criteria provided, single submitter clinical testing The p.T242I variant (also known as c.725C>T), located in coding exon 5 of the CHEK2 gene, results from a C to T substitution at nucleotide position 725. The threonine at codon 242 is replaced by isoleucine, an amino acid with similar properties. This alteration was identified in a cohort of 581 consecutive individuals with breast and/or ovarian cancer from Germany (Kraus C et al. Int J Cancer, 2017 Jan;140:95-102). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003225119 SCV003921668 uncertain significance not provided 2022-10-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with ovarian cancer (Kraus et al., 2017); This variant is associated with the following publications: (PMID: 22419737, 19782031, 27616075)

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