Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000693600 | SCV000821475 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 2300 of the ATM protein (p.Trp2300Gly). This variant is not present in population databases (gnomAD no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 572261). This missense change has been observed in individual(s) with ATM-related conditions (PMID: 33098801). |
| Color Diagnostics, |
RCV000772397 | SCV000905575 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-29 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics Munich, |
RCV000693600 | SCV001149687 | likely pathogenic | Ataxia-telangiectasia syndrome | 2019-02-21 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000772397 | SCV002667049 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-07 | criteria provided, single submitter | clinical testing | The p.W2300G variant (also known as c.6898T>G), located in coding exon 46 of the ATM gene, results from a T to G substitution at nucleotide position 6898. The tryptophan at codon 2300 is replaced by glycine, an amino acid with highly dissimilar properties. This alteration was identified in an individual with a personal and/or family history of breast and/or ovarian cancer (Lerner-Ellis J et al. J Cancer Res Clin Oncol, 2021 Mar;147:871-879). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Department of Pathology and Laboratory Medicine, |
RCV001356011 | SCV001551059 | uncertain significance | Malignant tumor of breast | no assertion criteria provided | clinical testing | The ATM p.Trp2300Gly variant was not identified in the literature nor was it identified in the dbSNP or LOVD 3.0 databases. The variant was only identified in ClinVar (classified as uncertain significance by Invitae). The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Trp2300 residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |