ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5459A>C (p.Lys1820Thr) (rs983664978)

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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 RCV000571509 SCV000667847 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000706129 SCV000835161 uncertain significance Ataxia-telangiectasia syndrome 2018-05-22 criteria provided, single submitter clinical testing This sequence change replaces lysine with threonine at codon 1820 of the ATM protein (p.Lys1820Thr). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and threonine. 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. ClinVar contains an entry for this variant (Variation ID: 482545). 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 and their clinical significance is uncertain. 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.
Integrated Genetics/Laboratory Corporation of America RCV000780887 SCV000918517 uncertain significance not specified 2017-10-06 criteria provided, single submitter clinical testing Variant summary: The ATM c.5459A>C (p.Lys1820Thr) variant involves the alteration of a non-conserved nucleotide. 2/3 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 215010 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.

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