ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5728C>A (p.Leu1910Ile) (rs143577586)

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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 RCV000165074 SCV000215776 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
Color RCV000165074 SCV000913969 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-09 criteria provided, single submitter clinical testing
Counsyl RCV000196827 SCV000800016 uncertain significance Ataxia-telangiectasia syndrome 2018-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000254907 SCV000322060 uncertain significance not provided 2018-12-12 criteria provided, single submitter clinical testing This variant is denoted ATM c.5728C>A at the cDNA level, p.Leu1910Ile (L1910I) at the protein level, and results in the change of a Leucine to an Isoleucine (CTT>ATT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. ATM Leu1910Ile 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 Leu1910Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000196827 SCV000254123 uncertain significance Ataxia-telangiectasia syndrome 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 1910 of the ATM protein (p.Leu1910Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is present in population databases (rs143577586, ExAC 0.002%). This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 185625). 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: "Probably 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.

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