Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159737 | SCV000209751 | uncertain significance | not provided | 2014-04-30 | criteria provided, single submitter | clinical testing | This variant is denoted ATM c.5677T>A at the cDNA level, p.Ser1893Thr (S1893T) at the protein level, and results in the change of a Serine to a Threonine (TCA>ACA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Ser1893Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Serine and Threonine share similar properties, this is considered a conservative amino acid substitution. ATM Ser1893Thr occurs at a position that is moderately conserved across species and is located at a site of autophosphorylation (Lavin 2008). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether ATM Ser1893Thr is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Labcorp Genetics |
RCV005055645 | SCV005713332 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-07-15 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1893 of the ATM protein (p.Ser1893Thr). 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: 181970). 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 tolerated. 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. |