ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1604G>A (p.Arg535His) (rs544216926)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212482 SCV000149917 uncertain significance not provided 2016-02-18 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.1604G>A at the cDNA level, p.Arg535His (R535H) at the protein level, and results in the change of an Arginine to a Histidine (CGC>CAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Although this variant was observed in 1000 Genomes, population data in this region of CHEK2 are not considered reliable due to high pseudogene homology. Since Arginine and Histidine share similar properties, this is considered a conservative amino acid substitution. CHEK2 Arg535His occurs at a position where amino acids with properties similar to Arginine are tolerated across species and is not located in a known functional domain (Roeb 2012, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether CHEK2 Arg535His is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000116008 SCV000213783 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000412260 SCV000489079 uncertain significance Familial cancer of breast 2016-08-15 criteria provided, single submitter clinical testing
Invitae RCV000212482 SCV000561008 likely benign not provided 2019-02-04 criteria provided, single submitter clinical testing
Color RCV000116008 SCV000910857 likely benign Hereditary cancer-predisposing syndrome 2017-06-22 criteria provided, single submitter clinical testing

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