ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1921_1923GAA[1] (p.Glu642del) (rs876659575)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218529 SCV000276187 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000218529 SCV000687345 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-10 criteria provided, single submitter clinical testing
GeneDx RCV000235502 SCV000293871 uncertain significance not provided 2018-12-06 criteria provided, single submitter clinical testing This in-frame deletion of 3 nucleotides in ATM is denoted c.1924_1926delGAA at the cDNA level and p.Glu642del (E642del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AGAA[delGAA]CTTT. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). This deletion of a single Glutamic Acid residue is not located in a known functional domain. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider ATM Glu642del to be a variant of uncertain significance.
Invitae RCV000529776 SCV000622294 uncertain significance Ataxia-telangiectasia syndrome 2018-11-22 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 13 of the ATM mRNA (c.1924_1926delGAA). This leads to the deletion of 1 amino acid residue in the ATM protein (p.Glu642del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 232133). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. In summary, this is a novel in-frame deletion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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