Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022900 | SCV001184693 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-21 | criteria provided, single submitter | clinical testing | The p.W156* pathogenic mutation (also known as c.468G>A), located in coding exon 4 of the ATM gene, results from a G to A substitution at nucleotide position 468. This changes the amino acid from a tryptophan to a stop codon within coding exon 4. This mutation was reported in a patient with ovarian cancer who tested negative for a BRCA2 mutation present in her family (Dominguez-Valentin M et al. Hered. Cancer Clin. Pract. 2018 Jan;16:4). In addition to the clinical data presented in the literature, 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. |
| Institute of Medical Genetics and Applied Genomics, |
RCV001543537 | SCV001762162 | pathogenic | not provided | 2021-06-17 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001862238 | SCV002152147 | pathogenic | Ataxia-telangiectasia syndrome | 2023-06-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 825099). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia and/or ovarian cancer (PMID: 24954719, 29371908). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp156*) 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). |