Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564940 | SCV000667883 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-02-09 | criteria provided, single submitter | clinical testing | The p.D211N variant (also known as c.631G>A), located in coding exon 5 of the ATM gene, results from a G to A substitution at nucleotide position 631. The aspartic acid at codon 211 is replaced by asparagine, 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 6498 samples (12996 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 125000 alleles tested) in our clinical cohort.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 alterationremains unclear. |
| Invitae | RCV000686289 | SCV000813801 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 211 of the ATM protein (p.Asp211Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 482566). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |