Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213841 | SCV000276549 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-03 | criteria provided, single submitter | clinical testing | The p.L1189F variant (also known as c.3565C>T), located in coding exon 23 of the ATM gene, results from a C to T substitution at nucleotide position 3565. The leucine at codon 1189 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was detected in 1/5589 German BRCA1/2-negative probands with breast cancer (Hauke J et al. Cancer Med, 2018 04;7:1349-1358). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000213841 | SCV000682139 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-11 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000699376 | SCV000828082 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1189 of the ATM protein (p.Leu1189Phe). This variant is present in population databases (rs370602633, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 232416). 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. |
| Gene |
RCV001753669 | SCV001985259 | uncertain significance | not provided | 2021-10-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29522266, 28652578) |
| Baylor Genetics | RCV003469056 | SCV004210194 | uncertain significance | Familial cancer of breast | 2023-07-06 | criteria provided, single submitter | clinical testing |