ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1067C>T (p.Ser356Leu) (rs121908703)

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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 RCV000132117 SCV000187184 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-26 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000474753 SCV000550480 uncertain significance Familial cancer of breast 2019-12-16 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 356 of the CHEK2 protein (p.Ser356Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs121908703, ExAC 0.003%). This variant has been observed in an individual affected with non-Hodgkin lymphoma (PMID: 26506619), and an individual affected with thyroid cancer (PMID: 29700698). ClinVar contains an entry for this variant (Variation ID: 126907). This variant has been reported to have conflicting or insufficient data to determine the effect on CHEK2 protein function (PMID: 30851065, 31050813). 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.
Color RCV000132117 SCV000684555 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-26 criteria provided, single submitter clinical testing
Counsyl RCV000474753 SCV000784926 uncertain significance Familial cancer of breast 2017-02-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781298 SCV000919217 uncertain significance not specified 2017-12-26 criteria provided, single submitter clinical testing Variant summary: The CHEK2 c.1067C>T (p.Ser356Leu) variant involves the alteration of a conserved nucleotide and is predicted to be damaging by 4/4 in silico tools (SNPsandGO not captured due to low reliability index). This variant was found in 4/215270 control chromosomes (gnomAD), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000036 (4/111556). This frequency is about 1.3 times the estimated maximal expected allele frequency of an LFS-causing CHEK2 variant (0.0000284), suggesting this may be a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. However, there are no other supporting evidences. This variant has been reported in one patient with non-Hodgkin Lymphoma (Havranek_2015). Multiple clinical diagnostic laboratories/reputable databases have classified this variant as uncertain significance. Taken together, this variant is classified as Variant of Unknown Significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000114763 SCV001245713 uncertain significance not provided 2019-10-01 criteria provided, single submitter clinical testing
Institute. of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague RCV000114763 SCV000148658 not provided not provided no assertion provided not provided

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