Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000566980 | SCV000667815 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-22 | criteria provided, single submitter | clinical testing | The p.M1006T variant (also known as c.3017T>C), located in coding exon 19 of the ATM gene, results from a T to C substitution at nucleotide position 3017. The methionine at codon 1006 is replaced by threonine, an amino acid with similar properties. 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. |
Labcorp Genetics |
RCV000812359 | SCV000952670 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-07-21 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 482532). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1006 of the ATM protein (p.Met1006Thr). |
Color Diagnostics, |
RCV000566980 | SCV001347608 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-27 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with threonine at codon 1006 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298678 | SCV002598815 | uncertain significance | not specified | 2022-09-25 | criteria provided, single submitter | clinical testing |