ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1231T>G (p.Trp411Gly)

dbSNP: rs587780172
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231745 SCV000289657 uncertain significance Familial cancer of breast 2023-08-07 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 240733). 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. 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. 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 tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 411 of the CHEK2 protein (p.Trp411Gly).
Color Diagnostics, LLC DBA Color Health RCV000580448 SCV000684573 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces tryptophan with glycine at codon 411 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). 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 RCV000580448 SCV001170664 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-28 criteria provided, single submitter clinical testing The p.W411G variant (also known as c.1231T>G), located in coding exon 10 of the CHEK2 gene, results from a T to G substitution at nucleotide position 1231. The tryptophan at codon 411 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000231745 SCV004217587 uncertain significance Familial cancer of breast 2023-08-25 criteria provided, single submitter clinical testing

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