ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1524del (p.Gly509fs) (rs786204737)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169584 SCV000221089 likely pathogenic Ataxia-telangiectasia syndrome 2015-01-27 criteria provided, single submitter literature only
GeneDx RCV000236634 SCV000293432 likely pathogenic not provided 2016-02-29 criteria provided, single submitter clinical testing This deletion of one nucleotide in ATM is denoted c.1524delT at the cDNA level and p.Gly509GlufsX3 (G509EfsX3) at the protein level. The normal sequence, with the base that is deleted in braces, is TACT[T]GGAG. The deletion causes a frameshift which changes a Glycine to a Glutamic Acid at codon 509, and creates a premature stop codon at position 3 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM c.1524delT, also published as ATM Leu508LeufsX4, has been observed in at least one individual with Ataxia Telangiectasia (Cavalieri 2008). Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Invitae RCV000169584 SCV000622267 pathogenic Ataxia-telangiectasia syndrome 2019-08-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly509Glufs*3) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with ataxia-telangiectasia (PMID: 16941484). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 189158) Loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000573650 SCV000665463 pathogenic Hereditary cancer-predisposing syndrome 2019-04-30 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Color RCV000573650 SCV001349858 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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