Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016427 | SCV001177383 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-25 | criteria provided, single submitter | clinical testing | The p.A911S variant (also known as c.2731G>T), located in coding exon 17 of the ATM gene, results from a G to T substitution at nucleotide position 2731. The alanine at codon 911 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in other 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. |
| Baylor Genetics | RCV003467629 | SCV004210301 | uncertain significance | Familial cancer of breast | 2023-06-05 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001016427 | SCV004360769 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-21 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 911 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). To our knowledge, functional studies have not been reported 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. |
| Invitae | RCV003605705 | SCV004449681 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-03-31 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 821729). 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 alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 911 of the ATM protein (p.Ala911Ser). 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 serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |