ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5509T>G (p.Phe1837Val) (rs876660472)

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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 RCV000215343 SCV000277932 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-13 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000486930 SCV000570490 uncertain significance not provided 2017-01-02 criteria provided, single submitter clinical testing This variant is denoted ATM c.5509T>G at the cDNA level, p.Phe1837Val (F1837V) at the protein level, and results in the change of a Phenylalanine to a Valine (TTT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Phe1837Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Phenylalanine and Valine differ in some properties, this is considered a semi-conservative amino acid substitution. ATM Phe1837Val occurs at a position where amino acids with properties similar to Phenylalanine are tolerated across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether ATM Phe1837Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000533648 SCV000622596 uncertain significance Ataxia-telangiectasia syndrome 2019-10-12 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with valine at codon 1837 of the ATM protein (p.Phe1837Val). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and valine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 233538). 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, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000215343 SCV000914022 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-05 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000486930 SCV001148435 uncertain significance not provided 2016-12-01 criteria provided, single submitter clinical testing

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