Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001234933 | SCV001407594 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-11-26 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1744 of the ATM protein (p.Lys1744Asn). 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: 961265). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM 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. |
Pittsburgh Clinical Genomics Laboratory, |
RCV001249856 | SCV001424018 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-12-17 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (G>C) that results in a lysine to asparagine amino acid change at residue 1744 in the ATM protein. This variant has not been reported in breast cancer patients in the literature, to our knowledge, and is not present in control population datasets (ExAC/gnomAD databases). The Lys1744 residue is not located in a functional domain and studies assessing the effects of this particular variant on ATM function have not been identified. Multiple bioinformatic tools queried predict that this lysine to asparagine amino acid change would be tolerated. The lysine at this position is conserved across most mammalian species examined, but is an arginine in the shrew and armadillo. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider the clinical significance of this variant to be uncertain. |