ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2655A>T (p.Leu885Phe) (rs730881351)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159700 SCV000209710 uncertain significance not provided 2017-03-09 criteria provided, single submitter clinical testing This variant is denoted ATM c.2655A>T at the cDNA level, p.Leu885Phe (L885F) at the protein level, and results in the change of a Leucine to a Phenylalanine (TTA>TTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Leu885Phe was not observed in large population cohorts (Lek 2016, The 1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). Since Leucine and Phenylalanine share similar properties, this is considered a conservative amino acid substitution. ATM Leu885Phe occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether ATM Leu885Phe is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000456359 SCV000546802 uncertain significance Ataxia-telangiectasia syndrome 2018-10-15 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 885 of the ATM protein (p.Leu885Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 181934). 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 C15"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000565271 SCV000665642 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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