Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001184682 | SCV001350718 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-21 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 1220 of the ATM protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer 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. |
| Labcorp Genetics |
RCV001337178 | SCV001530769 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-05-21 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 923758). 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. 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. This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1220 of the ATM protein (p.Glu1220Lys). |
| Ambry Genetics | RCV001184682 | SCV002617637 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-29 | criteria provided, single submitter | clinical testing | The p.E1220K variant (also known as c.3658G>A), located in coding exon 24 of the ATM gene, results from a G to A substitution at nucleotide position 3658. The glutamic acid at codon 1220 is replaced by lysine, an amino acid with similar properties. This alteration was observed in with an allele frequency of 0.00014 in 7,051 unselected female breast cancer patients and was not observed in 11,241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is highly 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. |