Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000159764 | SCV000209784 | uncertain significance | not provided | 2016-11-18 | criteria provided, single submitter | clinical testing | This variant is denoted ATM c.4070C>G at the cDNA level, p.Ser1357Cys (S1357C) at the protein level, and results in the change of a Serine to a Cysteine (TCT>TGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Ser1357Cys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Serine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Ser1357Cys occurs at a position that is not conserved and is not located in a known functional domain (Tavtigian 2009, Stracker 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether ATM Ser1357Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV000695377 | SCV000823872 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-05-01 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 181995). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is present in population databases (rs730881390, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1357 of the ATM protein (p.Ser1357Cys). |
Mendelics | RCV000695377 | SCV000838532 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing |