ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5549del (p.Leu1850fs) (rs876658287)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219889 SCV000273322 pathogenic Hereditary cancer-predisposing syndrome 2018-03-20 criteria provided, single submitter clinical testing The c.5549delT pathogenic mutation, located in coding exon 36 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 5549, causing a translational frameshift with a predicted alternate stop codon. This alteration has been reported in multiple individuals with Ataxia-Telangiectasia (Sandoval N et al, Hum. Mol. Genet. 1999 Jan; 8(1):69-79; Li A et al, Am. J. Med. Genet. 2000 May; 92(3):170-7; Castellví-Bel S et al, Hum. Mutat. 1999; 14(2):156-62). 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 RCV000236989 SCV000292817 pathogenic not provided 2020-01-30 criteria provided, single submitter clinical testing Frameshift 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 in individuals with a personal or family history consistent with pathogenic variants in this gene (Carter 2018); Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 30322717, 10425038, 26556299, 16266405, 9887333, 10817650, 29625052, 26689913)
Counsyl RCV000411540 SCV000486274 likely pathogenic Ataxia-telangiectasia syndrome 2016-04-28 criteria provided, single submitter clinical testing
Invitae RCV000411540 SCV001206115 pathogenic Ataxia-telangiectasia syndrome 2020-10-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1850Tyrfs*67) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs750992549, ExAC 0.002%). This variant has been observed to be homozygous in or in combination with another pathogenic ATM variant in several individuals affected with ataxia-telangiectasia (PMID: 9887333, 16266405, 10817650). It has also been observed as heterozygous in an individual with mesothelioma (PMID: 26556299). This variant is also known as 5546delT in the literature. ClinVar contains an entry for this variant (Variation ID: 229942). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Color Health, Inc RCV000219889 SCV001344865 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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