ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1317G>C (p.Gln439His)

dbSNP: rs878854915
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000457423 SCV000550435 uncertain significance Familial cancer of breast 2022-10-05 criteria provided, single submitter clinical testing 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 410006). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 439 of the CHEK2 protein (p.Gln439His).
Ambry Genetics RCV000570489 SCV000666347 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-17 criteria provided, single submitter clinical testing The p.Q439H variant (also known as c.1317G>C), located in coding exon 11 of the CHEK2 gene, results from a G to C substitution at nucleotide position 1317. The glutamine at codon 439 is replaced by histidine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 130000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. 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.
Counsyl RCV000457423 SCV000785053 uncertain significance Familial cancer of breast 2017-03-28 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000457423 SCV004020109 uncertain significance Familial cancer of breast 2023-03-08 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

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