Submissions for variant NM_000051.4(ATM):c.1179_1180del (p.Trp393_Glu394delinsTer)

dbSNP: rs876659450

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000219422	SCV000275938	pathogenic	Hereditary cancer-predisposing syndrome	2023-05-26	criteria provided, single submitter	clinical testing	The c.1179_1180delGG pathogenic mutation (also known as p.W393*), located in coding exon 8 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 1179 to 1180. This changes the amino acid from a tryptophan to a stop codon within coding exon 8. This mutation has been reported in conjunction with another ATM mutation in multiple individuals with ataxia telangiectasia (AT) (Teraoka SN et al. Am. J. Hum. Genet. 1999 Jun; 64(6):1617-31; Buzin CH et al. Hum. Mutat. 2003 Feb;21(2):123-31; Podralska MJ et al. Mol. Genet. Genomic Med. 2014 Nov;2(6):504-11). 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.
GeneDx	RCV000479095	SCV000568315	pathogenic	not provided	2022-12-16	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed with another pathogenic ATM variant in individuals with ataxia-telangiectasia (Teraoka et al., 1999; Chun et al., 2002; Buzin et al., 2003; Podralska et al., 2014); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25614872, 10330348, 16461462, 11857346, 12552559)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588480	SCV000694173	pathogenic	Ataxia-telangiectasia syndrome	2016-01-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000588480	SCV000828812	pathogenic	Ataxia-telangiectasia syndrome	2023-12-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp393*) 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 premature translational stop signal has been observed in individual(s) with ataxia telangiectasia (PMID: 10330348, 10873394, 12552559). ClinVar contains an entry for this variant (Variation ID: 231937). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000219422	SCV001340965	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 9 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001252971	SCV001428453	likely pathogenic	Familial cancer of breast	2019-04-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001252971	SCV004207736	pathogenic	Familial cancer of breast	2023-08-21	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001252971	SCV004932209	pathogenic	Familial cancer of breast	2024-01-12	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.
Natera, Inc.	RCV000588480	SCV001456884	pathogenic	Ataxia-telangiectasia syndrome	2020-09-16	no assertion criteria provided	clinical testing