Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000657354 | SCV000779086 | likely pathogenic | not provided | 2017-07-17 | criteria provided, single submitter | clinical testing | This deletion of four nucleotides in ATM is denoted c.1285_1288delAACT at the cDNA level and p.Asn429ValfsX7 (N429VfsX7) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACCT[delAACT]GTGA. The deletion causes a frameshift which changes an Asparagine to a Valine at codon 429, and creates a premature stop codon at position 7 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant. |
Invitae | RCV001861677 | SCV002179759 | pathogenic | Ataxia-telangiectasia syndrome | 2022-08-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn429Valfs*7) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 545804). This premature translational stop signal has been observed in individual(s) with a pancreatic tumor (PMID: 29506128). This variant is not present in population databases (gnomAD no frequency). |
Myriad Genetics, |
RCV004026000 | SCV004932819 | pathogenic | Familial cancer of breast | 2024-01-16 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |