Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000570543 | SCV000667973 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-02-14 | criteria provided, single submitter | clinical testing | The p.L121* pathogenic mutation (also known as c.362T>A), located in coding exon 4 of the ATM gene, results from a T to A substitution at nucleotide position 362. This changes the amino acid from a leucine to a stop codon within coding exon 4. This mutation has been identified in conjunction with another pathogenic ATM mutation in multiple patients diagnosed with ataxia-telangiectasia (Birrell GW et al. Hum. Mutat., 2005 Jun;25:593; Demuth I et al. Neurogenetics, 2011 Nov;12:273-82). 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. |
Invitae | RCV001858239 | SCV002152142 | pathogenic | Ataxia-telangiectasia syndrome | 2022-10-16 | 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: 482626). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia and pancreatic adenocarcinoma (PMID: 15880721, 21965147, 29625052). This variant is present in population databases (rs771342315, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Leu121*) 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). |
Myriad Genetics, |
RCV004024497 | SCV004931602 | pathogenic | Familial cancer of breast | 2024-01-09 | 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. |