Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000627973 | SCV000748860 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-02-20 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1801 of the ATM protein (p.Asn1801Ser). 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: 524295). 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. |
| Ambry Genetics | RCV001024041 | SCV001185994 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-28 | criteria provided, single submitter | clinical testing | The p.N1801S variant (also known as c.5402A>G), located in coding exon 35 of the ATM gene, results from an A to G substitution at nucleotide position 5402. The asparagine at codon 1801 is replaced by serine, an amino acid with highly similar properties. This amino acid position is poorly 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235316 | SCV003934439 | uncertain significance | not specified | 2023-05-06 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001355769 | SCV001550741 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The ATM p.Asn1801Ser variant was not identified in the literature nor was it identified in the following databases: dbSNP, ClinVar, COGR, Cosmic, MutDB, LOVD 3.0, or ATM-LOVD. The variant was not identified in control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Asn1801 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. 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. |