ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.896T>C (p.Ile299Thr)

dbSNP: rs876659870
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000584218 SCV000689739 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-06 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 299 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001215586 SCV001387338 uncertain significance Familial cancer of breast 2023-03-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 299 of the CHEK2 protein (p.Ile299Thr). 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: 491652). 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. 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.
Ambry Genetics RCV000584218 SCV002683680 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-29 criteria provided, single submitter clinical testing The p.I299T variant (also known as c.896T>C), located in coding exon 7 of the CHEK2 gene, results from a T to C substitution at nucleotide position 896. The isoleucine at codon 299 is replaced by threonine, an amino acid with similar 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 RCV001215586 SCV005058390 uncertain significance Familial cancer of breast 2024-01-08 criteria provided, single submitter clinical testing

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