ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1312G>C (p.Asp438His)

dbSNP: rs200050883
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000580180 SCV000684581 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000580180 SCV001171179 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-29 criteria provided, single submitter clinical testing The p.D438H variant (also known as c.1312G>C), located in coding exon 11 of the CHEK2 gene, results from a G to C substitution at nucleotide position 1312. The aspartic acid at codon 438 is replaced by histidine, an amino acid with similar properties. This amino acid position is 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 RCV002529097 SCV003353348 uncertain significance Familial cancer of breast 2022-04-18 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 438 of the CHEK2 protein (p.Asp438His). This variant is not present in population databases (gnomAD no frequency). 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: 489878). 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"). 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.

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