Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000226250 | SCV000282992 | pathogenic | Ataxia-telangiectasia syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp1815Thrfs*13) 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 present in population databases (rs772138812, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 26689913). ClinVar contains an entry for this variant (Variation ID: 236738). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV004020737 | SCV004933585 | pathogenic | Familial cancer of breast | 2024-01-25 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Department of Pathology and Laboratory Medicine, |
RCV001357161 | SCV001552534 | pathogenic | Carcinoma of colon | no assertion criteria provided | clinical testing | The ATM p.Asp1815Thrfs*13 variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (ID: rs878853522) as "With Pathogenic allele" and in ClinVar (classified as pathogenic by Invitae). The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The c.5443del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1815 and leads to a premature stop codon at position 1827. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the ATM gene are an established mechanism of disease in ATM-associated cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. |