Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV003492141 | SCV000838495 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000709168 | SCV001545301 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-10-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 609 of the ATM protein (p.Glu609Gln). This variant is present in population databases (rs779780896, gnomAD 0.0009%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 584779). 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 tolerated. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
MGZ Medical Genetics Center | RCV002289985 | SCV002579852 | uncertain significance | Familial cancer of breast | 2022-01-27 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002406652 | SCV002712089 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-26 | criteria provided, single submitter | clinical testing | The p.E609Q variant (also known as c.1825G>C), located in coding exon 11 of the ATM gene, results from a G to C substitution at nucleotide position 1825. The glutamic acid at codon 609 is replaced by glutamine, an amino acid with highly similar properties. In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet, 2018 04;14:e1007352). 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. |
Natera, |
RCV000709168 | SCV002076122 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-10-09 | no assertion criteria provided | clinical testing |