Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130916 | SCV000185826 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-16 | criteria provided, single submitter | clinical testing | The p.E2374A variant (also known as c.7121A>C), located in coding exon 48 of the ATM gene, results from an A to C substitution at nucleotide position 7121. The glutamic acid at codon 2374 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is not well 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. |
| Labcorp Genetics |
RCV000698695 | SCV000827375 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with alanine at codon 2374 of the ATM protein (p.Glu2374Ala). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 142089). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Fulgent Genetics, |
RCV002492507 | SCV002785376 | uncertain significance | Familial cancer of breast; Ataxia-telangiectasia syndrome | 2022-05-12 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000130916 | SCV004361832 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with alanine at codon 2374 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-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. |
| Baylor Genetics | RCV004567124 | SCV005053043 | uncertain significance | Familial cancer of breast | 2023-11-08 | criteria provided, single submitter | clinical testing |