Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000688968 | SCV000816600 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-11-28 | criteria provided, single submitter | clinical testing | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ATM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 3007 of the ATM protein (p.Glu3007Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. |
| Institute of Human Genetics, |
RCV001253737 | SCV001429593 | uncertain significance | Familial cancer of breast | 2018-12-06 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002369847 | SCV002686325 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-10-05 | criteria provided, single submitter | clinical testing | The p.E3007D variant (also known as c.9021A>C), located in coding exon 62 of the ATM gene, results from an A to C substitution at nucleotide position 9021. The glutamic acid at codon 3007 is replaced by aspartic acid, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 66000 alleles tested) in our clinical cohort. 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 p.E3007D remains unclear. |