ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3836G>A (p.Trp1279Ter)

dbSNP: rs587779836
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212003 SCV000149090 pathogenic not provided 2017-10-09 criteria provided, single submitter clinical testing This variant is denoted ATM c.3836G>A at the cDNA level and p.Trp1279Ter (W1279X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in the compound heterozygous state in an individual with ataxia-telangiectasia (Mitui 2003) and is considered pathogenic.
Ambry Genetics RCV000115181 SCV000184283 pathogenic Hereditary cancer-predisposing syndrome 2023-02-28 criteria provided, single submitter clinical testing The p.W1279* pathogenic mutation (also known as c.3836G>A), located in coding exon 25 of the ATM gene, results from a G to A substitution at nucleotide position 3836. This changes the amino acid from a tryptophan to a stop codon within coding exon 25. This alteration has been reported in conjunction with a second truncating mutation in an individual with ataxia telangiectasia (AT) (Mitui M et al. Hum. Mutat. 2003; 22:43-50). In addition to the information presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV001274265 SCV001586483 pathogenic Ataxia-telangiectasia syndrome 2023-11-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1279*) 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 clinical features of ataxia telangiectasia (PMID: 12815592). ClinVar contains an entry for this variant (Variation ID: 127376). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV004019606 SCV004931179 pathogenic Familial cancer of breast 2024-01-23 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.
Baylor Genetics RCV004019606 SCV005056984 pathogenic Familial cancer of breast 2024-02-15 criteria provided, single submitter clinical testing
Natera, Inc. RCV001274265 SCV001458196 pathogenic Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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