ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1010G>A (p.Arg337His) (rs202160435)

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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 RCV000115131 SCV000187478 likely benign Hereditary cancer-predisposing syndrome 2018-03-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other strong data supporting benign classification,Subpopulation frequency in support of benign classification,Other data supporting benign classification
Color RCV000115131 SCV000681944 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing
GeneDx RCV000211955 SCV000149040 uncertain significance not provided 2018-12-20 criteria provided, single submitter clinical testing This variant is denoted ATM c.1010G>A at the cDNA level, p.Arg337His (R337H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant has been observed in at least four individuals with breast cancer (Tung 2015, Decker 2017, Hauke 2018). ATM Arg337His was observed at an allele frequency of 0.014% (15/111,508) in individuals of European ancestry 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 Arg337His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000204640 SCV000260740 uncertain significance Ataxia-telangiectasia syndrome 2018-06-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 337 of the ATM protein (p.Arg337His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs202160435, ExAC 0.02%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 127328). 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.
Mendelics RCV000204640 SCV000838479 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing

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