Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000575328 | SCV000665406 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-07 | criteria provided, single submitter | clinical testing | The c.1039_1040delGAinsTT variant (also known as p.E347L), located in coding exon 7 of the ATM gene, results from an in-frame deletion of GA and insertion of TT at nucleotide positions 1039 to 1040. This results in the substitution of the glutamic acid residue for a leucine residue at codon 347, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000700077 | SCV000828817 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with leucine, which is neutral and non-polar, at codon 347 of the ATM protein (p.Glu347Leu). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. 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: 481181). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Gene |
RCV003159960 | SCV003914998 | uncertain significance | not provided | 2022-10-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge |