Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569717 | SCV000665279 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-28 | criteria provided, single submitter | clinical testing | The p.E166D variant (also known as c.498A>T), located in coding exon 5 of the ATM gene, results from an A to T substitution at nucleotide position 498. The glutamic acid at codon 166 is replaced by aspartic acid, an amino acid with highly similar properties. This variant was observed in a study of 1010 unrelated Indian patients with breast and/or ovarian cancer (Singh J et al. Breast Cancer Res Treat. 2018 Jul;170:189-196). This amino acid position is 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 |
RCV000627997 | SCV000748884 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 166 of the ATM protein (p.Glu166Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with breast and/or ovarian cancer patient (PMID: 29470806). ClinVar contains an entry for this variant (Variation ID: 481115). 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. 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. |
| Color Diagnostics, |
RCV000569717 | SCV000904430 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with aspartic acid at codon 166 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 been reported in an individual affected with breast and/or ovarian cancer (PMID: 29470806). 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. |
| Mendelics | RCV000627997 | SCV001138432 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003459313 | SCV004213906 | uncertain significance | Familial cancer of breast | 2022-04-12 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000627997 | SCV002093985 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-03-30 | no assertion criteria provided | clinical testing |