ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.7816A>G (p.Ile2606Val) (rs376824528)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166765 SCV000217578 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513206 SCV000608619 uncertain significance not provided 2017-04-30 criteria provided, single submitter clinical testing
Color RCV000166765 SCV000902970 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-25 criteria provided, single submitter clinical testing
GeneDx RCV000513206 SCV000564661 uncertain significance not provided 2018-05-14 criteria provided, single submitter clinical testing This variant is denoted ATM c.7816A>G at the cDNA level, p.Ile2606Val (I2606V) at the protein level, and results in the change of an Isoleucine to a Valine (ATA>GTA). This variant has been reported in at least one individual with breast cancer (Tung 2015). ATM Ile2606Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Ile2606Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000625763 SCV000746305 likely pathogenic Hereditary breast and ovarian cancer syndrome 2017-12-03 criteria provided, single submitter clinical testing
Invitae RCV000197716 SCV000254152 uncertain significance Ataxia-telangiectasia syndrome 2018-06-29 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 2606 of the ATM protein (p.Ile2606Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs376824528, ExAC 0.003%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 187077). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000197716 SCV000838598 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
PreventionGenetics RCV000513206 SCV000805619 uncertain significance not provided 2017-09-08 criteria provided, single submitter clinical testing

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