Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000223003 | SCV000275126 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-11-06 | criteria provided, single submitter | clinical testing | The p.I773L variant (also known as c.2317A>C), located in coding exon 14 of the ATM gene, results from an A to C substitution at nucleotide position 2317. The isoleucine at codon 773 is replaced by leucine, 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 125000 alleles tested) in our clinical cohort. 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 p.I773L remains unclear. |
| Labcorp Genetics |
RCV000543166 | SCV000622321 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-01-08 | criteria provided, single submitter | clinical testing | In summary, this variant has uncertain impact on ATM function. The available evidence is currently insufficient to determine its role 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 (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. This variant has not been reported in the literature in individuals with a ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 231315). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with leucine at codon 773 of the ATM protein (p.Ile773Leu). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and leucine. |