ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2539A>T (p.Met847Leu) (rs587779823)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216310 SCV000275963 uncertain significance Hereditary cancer-predisposing syndrome 2015-05-26 criteria provided, single submitter clinical testing in silico models in agreement (benign);Insufficient or Conflicting Evidence;Co-occurence with mutation in same gene (phase unknown)
Invitae RCV000545371 SCV000622338 uncertain significance Ataxia-telangiectasia syndrome 2018-04-25 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 847 of the ATM protein (p.Met847Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease but has been observed in an individual with breast cancer and an individual with goiter and colon polyps (Invitae), neither of whom had features associated with ataxia-telangiectasia. In these individuals, a pathogenic allele was also identified in ATM, which suggests that this c.2539A>T variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 231957). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. 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 RCV000216310 SCV001345628 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-13 criteria provided, single submitter clinical testing

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