Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001201849 | SCV001372940 | pathogenic | Ataxia-telangiectasia syndrome | 2023-05-22 | 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: 933605). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu1224*) 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 | RCV003284038 | SCV004007284 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-16 | criteria provided, single submitter | clinical testing | The c.3669_3670insTAG pathogenic mutation (also known as p.L1224*), located in coding exon 24 of the ATM gene, results from an in-frame TAG insertion at nucleotide positions 3669 to 3670. This changes the amino acid from a leucine to a stop codon within coding exon 24. This mutation was identified in an individual with cholangiocarcinoma diagnosed at age 36 (Maynard H et al. Cancer, 2020 Jan;126:1995-2002). 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-mediatedmRNAdecay.As such, this alteration is interpreted as a disease-causing mutation. |