ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3341A>G (p.Lys1114Arg)

dbSNP: rs777705500
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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 RCV000221075 SCV000275432 likely benign Hereditary cancer-predisposing syndrome 2019-03-24 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000481285 SCV000566269 uncertain significance not provided 2023-07-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer (Knappskog et al., 2012); Published functional studies demonstrate slightly reduced ATM ubiquitination compared to wildtype (Kim et al., 2017); This variant is associated with the following publications: (PMID: 19781682, 22420423, 27958289)
Labcorp Genetics (formerly Invitae), Labcorp RCV000524647 SCV000622411 uncertain significance Ataxia-telangiectasia syndrome 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1114 of the ATM protein (p.Lys1114Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 22420423). ClinVar contains an entry for this variant (Variation ID: 231546). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Color Diagnostics, LLC DBA Color Health RCV000221075 SCV001342834 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-02 criteria provided, single submitter clinical testing This missense variant replaces lysine with arginine at codon 1114 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 22420423). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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