Submissions for variant NM_000051.4(ATM):c.1333del (p.Gln445fs)

dbSNP: rs1060501701

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000465109	SCV000547132	pathogenic	Ataxia-telangiectasia syndrome	2023-10-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln445Asnfs*28) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 407721). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000572783	SCV000667999	pathogenic	Hereditary cancer-predisposing syndrome	2021-10-04	criteria provided, single submitter	clinical testing	The c.1333delC pathogenic mutation, located in coding exon 9 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 1333, causing a translational frameshift with a predicted alternate stop codon (p.Q445Nfs*28). One study detected this mutation in 1/3030 pancreatic cancer cases and 0/123136 population controls (Hu C et al. JAMA, 2018 06;319:2401-2409). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV002467448	SCV002762771	pathogenic	Familial cancer of breast	2022-12-09	criteria provided, single submitter	research	PVS1, PM2_SUP, PM3_SUP
Baylor Genetics	RCV002467448	SCV004210182	likely pathogenic	Familial cancer of breast	2023-07-10	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV002467448	SCV004933146	pathogenic	Familial cancer of breast	2024-01-16	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.