Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000777525 | SCV000913388 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000777525 | SCV002655273 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-29 | criteria provided, single submitter | clinical testing | The p.L2128S variant (also known as c.6383T>C), located in coding exon 43 of the ATM gene, results from a T to C substitution at nucleotide position 6383. The leucine at codon 2128 is replaced by serine, an amino acid with dissimilar properties. This alteration was observed with an allele frequency of 0 in 7,051 unselected female breast cancer patients and was observed with an allele frequency of 0.00009 in 11,241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is well 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. |
| Gene |
RCV003318636 | SCV004022803 | uncertain significance | not provided | 2023-07-31 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in any cases, but was observed in unaffected controls from a breast cancer study (Momozawa et al., 2018); This variant is associated with the following publications: (PMID: 23532176, 30287823) |
| Labcorp Genetics |
RCV003607356 | SCV004551676 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2128 of the ATM protein (p.Leu2128Ser). This variant is not present in population databases (gnomAD no frequency). 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: 631338). 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. |