Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000804810 | SCV000944741 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 940 of the ATM protein (p.Lys940Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 649794). 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 | RCV001016676 | SCV001177656 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-08 | criteria provided, single submitter | clinical testing | The p.K940T variant (also known as c.2819A>C), located in coding exon 17 of the ATM gene, results from an A to C substitution at nucleotide position 2819. The lysine at codon 940 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797799 | SCV002041610 | uncertain significance | not specified | 2021-11-08 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.2819A>C (p.Lys940Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251380 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge c.2819A>C has not been reported in the literature in individuals affected with Breast Cancer but has been reported in one individual affected with colorectal cancer (Yurgelun_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Mendelics | RCV001797799 | SCV002516953 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003467406 | SCV004209454 | uncertain significance | Familial cancer of breast | 2023-09-13 | criteria provided, single submitter | clinical testing |