ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1007A>C (p.Gln336Pro)

dbSNP: rs1300388084
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568852 SCV000661702 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-29 criteria provided, single submitter clinical testing The p.Q336P variant (also known as c.1007A>C), located in coding exon 8 of the CHEK2 gene, results from an A to C substitution at nucleotide position 1007. The glutamine at codon 336 is replaced by proline, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. 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.
Invitae RCV000689455 SCV000817106 uncertain significance Familial cancer of breast 2023-10-05 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 336 of the CHEK2 protein (p.Gln336Pro). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 479536). 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.
Color Diagnostics, LLC DBA Color Health RCV000568852 SCV004361362 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-22 criteria provided, single submitter clinical testing This missense variant replaces glutamine with proline at codon 336 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 1/251450 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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