Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000464991 | SCV000546843 | pathogenic | Ataxia-telangiectasia syndrome | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu647*) 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). 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: 407556). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000567510 | SCV000668124 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-14 | criteria provided, single submitter | clinical testing | The p.E647* pathogenic mutation (also known as c.1939G>T), located in coding exon 12 of the ATM gene, results from a G to T substitution at nucleotide position 1939. This changes the amino acid from a glutamic acid to a stop codon within coding exon 12. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Gene |
RCV000657762 | SCV000779515 | pathogenic | not provided | 2018-03-29 | criteria provided, single submitter | clinical testing | This variant is denoted ATM c.1939G>T at the cDNA level and p.Glu647Ter (E647X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic. |
| Myriad Genetics, |
RCV004022646 | SCV004933941 | pathogenic | Familial cancer of breast | 2024-01-17 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| Laboratory for Genotyping Development, |
RCV003168781 | SCV002758082 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |