Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019341 | SCV001180686 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-25 | criteria provided, single submitter | clinical testing | The p.F1077L variant (also known as c.3231T>A), located in coding exon 21 of the ATM gene, results from a T to A substitution at nucleotide position 3231. The phenylalanine at codon 1077 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001042887 | SCV001206595 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1077 of the ATM protein (p.Phe1077Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 823247). 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. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001264580 | SCV001442803 | uncertain significance | not specified | 2020-10-15 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.3231T>A (p.Phe1077Leu) 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 251296 control chromosomes. 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.3231T>A in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Baylor Genetics | RCV003467652 | SCV004210275 | uncertain significance | Familial cancer of breast | 2023-06-14 | criteria provided, single submitter | clinical testing |