Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001236897 | SCV001409638 | pathogenic | Ataxia-telangiectasia syndrome | 2021-06-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 962949). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser470*) 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). |
| Ambry Genetics | RCV003166469 | SCV003868864 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-08 | criteria provided, single submitter | clinical testing | The c.1409C>G pathogenic mutation (also known as p.S470*), located in coding exon 9 of the ATM gene, results from a C to G substitution at nucleotide position 1409. This changes the amino acid from a serine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, in silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. This nucleotide position is well conserved in available vertebrate species. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay; however, direct evidence is insufficient at this time (Ambry internal data). The exact functional effect of the altered amino acid sequence is unknown. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. |