ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.548T>C (p.Leu183Ser)

dbSNP: rs2053939966
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001192013 SCV001359956 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-14 criteria provided, single submitter clinical testing This missense variant replaces leucine with serine at codon 183 of the CHEK2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant has defective DNA damage response in a yeast assay (PMID: 30851065). This variant has been reported in individuals affected with breast cancer (PMID: 30851065). 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.
Invitae RCV003607417 SCV004509632 uncertain significance Familial cancer of breast 2023-03-14 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. Experimental studies have shown that this missense change affects CHEK2 function (PMID: 30851065). 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. ClinVar contains an entry for this variant (Variation ID: 928240). 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 leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 183 of the CHEK2 protein (p.Leu183Ser).

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