Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131714 | SCV000186752 | uncertain significance | Hereditary cancer-predisposing syndrome | 2013-06-28 | criteria provided, single submitter | clinical testing | The p.N344Y variant (also known as c.1030A>T) is located in exon 8 of the ATM gene. This alteration results from a A to T substitution at nucleotide position 1030. The asparagine at codon 344 is replaced by tyrosine, an amino acid with dissimilar properties.This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project.To date, this alteration has been detected with an allele frequency of approximately 0.03% (greater than 3500 alleles tested) in our clinical cohort (includes this individual). Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively.Since supporting evidence is limited at this time, the clinical significance ofp.N344Yremains unclear.​ |
| Labcorp Genetics |
RCV000808748 | SCV000948866 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with tyrosine at codon 344 of the ATM protein (p.Asn344Tyr). The asparagine residue is moderately conserved and there is a large physicochemical difference between asparagine and tyrosine. This variant is not present in population databases (ExAC 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: 142532). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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. |
| Color Diagnostics, |
RCV000131714 | SCV001344532 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-02 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with tyrosine at codon 344 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 ATM-related disorders 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. |
| Gene |
RCV004760395 | SCV005369210 | uncertain significance | not provided | 2023-07-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |