Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000216470 | SCV000278104 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-21 | criteria provided, single submitter | clinical testing | The p.L1282I variant (also known as c.3844C>A), located in coding exon 25 of the ATM gene, results from a C to A substitution at nucleotide position 3844. The leucine at codon 1282 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been reported in at least one subject in a study of 13087 breast cancer cases and 5488 control individuals in the UK (Decker B et al. J Med Genet, 2017 11;54:732-741). This variant was also reported in 1/5560 prostate cancer cases and in 0/3353 controls of European ancestry (Karlsson Q et al. Eur Urol Oncol, 2021 Aug;4:570-579). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV000540571 | SCV000622458 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-06-04 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 233679). This missense change has been observed in individual(s) with prostate cancer (PMID: 33436325). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1282 of the ATM protein (p.Leu1282Ile). 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 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. |
Baylor Genetics | RCV003469084 | SCV004210167 | uncertain significance | Familial cancer of breast | 2023-07-13 | criteria provided, single submitter | clinical testing |