ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.400G>C (p.Asp134His) (rs372874441)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212415 SCV000149922 uncertain significance not provided 2020-03-10 criteria provided, single submitter clinical testing Observed in an individual with colon cancer (You 2019); Published functional studies demonstrate no damaging effect: normal cell growth after DNA damage (Delimitsou 2019); Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30730459, 30851065)
Ambry Genetics RCV000116013 SCV000184367 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-05 criteria provided, single submitter clinical testing The p.D134H variant (also known as c.400G>C), located in coding exon 2 of the CHEK2 gene, results from a G to C substitution at nucleotide position 400. The aspartic acid at codon 134 is replaced by histidine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000473822 SCV000550526 uncertain significance Familial cancer of breast 2020-10-08 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 134 of the CHEK2 protein (p.Asp134His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs372874441, ExAC 0.001%). This variant has been observed in an individual affected with colorectal cancer (PMID: 30730459). ClinVar contains an entry for this variant (Variation ID: 128072). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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.
Mendelics RCV000473822 SCV000839493 uncertain significance Familial cancer of breast 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765625 SCV000896950 uncertain significance Familial cancer of breast; Li-Fraumeni syndrome 2; Bone osteosarcoma; Malignant tumor of prostate 2018-10-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV000116013 SCV001349570 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-16 criteria provided, single submitter clinical testing

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