Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001201198 | SCV001372272 | uncertain significance | not specified | 2020-06-29 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.4727T>C (p.Ile1576Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250980 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4727T>C in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002339499 | SCV002638302 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-05 | criteria provided, single submitter | clinical testing | The p.I1576T variant (also known as c.4727T>C), located in coding exon 30 of the ATM gene, results from a T to C substitution at nucleotide position 4727. The isoleucine at codon 1576 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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. |