Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479596 | SCV000564640 | uncertain significance | not provided | 2015-11-06 | criteria provided, single submitter | clinical testing | This variant is denoted ATM c.4440_4441delTTinsGC at the cDNA level and p.Ser1481Pro (S1481P) at the protein level. The normal sequence, with the bases that are deleted in braces and inserted in brackets, is gGCC[TT][GC]CTTG. This in frame deletion and insertion occurs on the same allele (in cis) and results in the missense change of a Serine to a Proline (TCT>CCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Neither ATM c.4440_4441delTTinsGC nor ATM Ser1481Pro (by this or an alternate nucleotide change) was 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 Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Ser1481Pro occurs at a position that is not conserved and is not located in a known functional domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether ATM Ser1481Pro is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV002298612 | SCV002592405 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-09-27 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 418033). This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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 sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1481 of the ATM protein (p.Ser1481Pro). |
| Fulgent Genetics, |
RCV002489141 | SCV002800795 | uncertain significance | Familial cancer of breast; Ataxia-telangiectasia syndrome | 2021-09-23 | criteria provided, single submitter | clinical testing |