ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.60G>T (p.Gln20His)

gnomAD frequency: 0.00002  dbSNP: rs375507194
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000635741 SCV000757163 uncertain significance Familial cancer of breast 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 20 of the CHEK2 protein (p.Gln20His). This variant is present in population databases (rs375507194, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 530100). 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. 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.
Ambry Genetics RCV001024901 SCV001186994 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-04 criteria provided, single submitter clinical testing The p.Q20H variant (also known as c.60G>T), located in coding exon 1 of the CHEK2 gene, results from a G to T substitution at nucleotide position 60. The glutamine at codon 20 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved on limited sequence alignment. 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.
Color Diagnostics, LLC DBA Color Health RCV001024901 SCV002052134 uncertain significance Hereditary cancer-predisposing syndrome 2021-03-22 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 20 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 5/247566 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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