ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.336C>G (p.Asn112Lys)

dbSNP: rs1060502689
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459664 SCV000550441 uncertain significance Familial cancer of breast 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 112 of the CHEK2 protein (p.Asn112Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 34326862, 35264596). ClinVar contains an entry for this variant (Variation ID: 410010). 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 tolerated. 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 RCV000459664 SCV000839496 uncertain significance Familial cancer of breast 2018-07-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000775719 SCV000910139 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-30 criteria provided, single submitter clinical testing This missense variant replaces asparagine with lysine at codon 112 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 CHEK2-related disorders in the literature. This variant has not been identified 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.
Ambry Genetics RCV000775719 SCV001181545 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-08 criteria provided, single submitter clinical testing The p.N112K variant (also known as c.336C>G), located in coding exon 2 of the CHEK2 gene, results from a C to G substitution at nucleotide position 336. The asparagine at codon 112 is replaced by lysine, 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.

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