ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.391A>G (p.Lys131Glu)

gnomAD frequency: 0.00001  dbSNP: rs1275395933
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000698440 SCV000827103 uncertain significance Familial cancer of breast 2022-12-20 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. ClinVar contains an entry for this variant (Variation ID: 576044). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 131 of the CHEK2 protein (p.Lys131Glu).
Color Diagnostics, LLC DBA Color Health RCV001183321 SCV001349034 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-25 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 131 of the CHEK2 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer 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 RCV001183321 SCV002624840 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-13 criteria provided, single submitter clinical testing The p.K131E variant (also known as c.391A>G), located in coding exon 2 of the CHEK2 gene, results from an A to G substitution at nucleotide position 391. The lysine at codon 131 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. 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.
Baylor Genetics RCV000698440 SCV004217569 uncertain significance Familial cancer of breast 2023-09-06 criteria provided, single submitter clinical testing

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