Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001982570 | SCV002222683 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-10-03 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 1700 of the ATM protein (p.Leu1700Arg). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and arginine. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. |