ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5039C>T (p.Pro1680Leu) (rs587782153)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130731 SCV000185622 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000205355 SCV000260511 uncertain significance Ataxia-telangiectasia syndrome 2018-06-06 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1680 of the ATM protein (p.Pro1680Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs587782153, ExAC 0.009%). This variant has been observed in an individual affected with breast and/or ovarian cancer (PMID: 28528518). ClinVar contains an entry for this variant (Variation ID: 141976). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV000481018 SCV000568012 uncertain significance not provided 2018-10-23 criteria provided, single submitter clinical testing This variant is denoted ATM c.5039C>T at the cDNA level, p.Pro1680Leu (P1680L) at the protein level, and results in the change of a Proline to a Leucine (CCT>CTT). This variant has been observed in at least one individual with breast and/or ovarian cancer (Cock-Rada 2018). ATM Pro1680Leu 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 a deleterious effect. Based on currently available evidence, it is unclear whether ATM Pro1680Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000130731 SCV000682243 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-20 criteria provided, single submitter clinical testing
Counsyl RCV000205355 SCV000796964 uncertain significance Ataxia-telangiectasia syndrome 2018-01-05 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.