ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3964C>A (p.Leu1322Ile) (rs144535256)

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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 RCV000132364 SCV000187454 likely benign Hereditary cancer-predisposing syndrome 2018-02-28 criteria provided, single submitter clinical testing Intact protein function observed in appropriate functional assay(s)
Invitae RCV000204555 SCV000259593 uncertain significance Ataxia-telangiectasia syndrome 2020-10-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 1322 of the ATM protein (p.Leu1322Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is present in population databases (rs144535256, ExAC 0.005%). This variant has been reported in an individual affected with endometrial carcinoma (PMID: 26689913). ClinVar contains an entry for this variant (Variation ID: 142896). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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 RCV000237005 SCV000293003 uncertain significance not provided 2020-01-13 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Published functional studies demonstrate no damaging effect: normal protein expression and kinase activity (Barone 2009); This variant is associated with the following publications: (PMID: 26689913, 28652578, 16014569, 19431188, 29684080)
Counsyl RCV000204555 SCV000795641 uncertain significance Ataxia-telangiectasia syndrome 2017-11-10 criteria provided, single submitter clinical testing
Color Health, Inc RCV000132364 SCV000906587 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-07 criteria provided, single submitter clinical testing

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