ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5653A>T (p.Thr1885Ser) (rs587779850)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213673 SCV000273970 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000213673 SCV000687633 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-18 criteria provided, single submitter clinical testing
GeneDx RCV000115215 SCV000149124 uncertain significance not provided 2015-01-30 criteria provided, single submitter clinical testing This variant is denoted ATM c.5653A>T at the cDNA level, p.Thr1885Ser (T1885S) at the protein level, and results in the change of a Threonine to a Serine (ACC>TCC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Thr1885Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Threonine and Serine share similar properties, this is considered a conservative amino acid substitution. ATM Thr1885Ser occurs at a position that is well conserved throughout evolution and is located in an Armadillo-type fold (Interpro). In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether ATM Thr1885Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000687995 SCV000815590 uncertain significance Ataxia-telangiectasia syndrome 2018-09-27 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 1885 of the ATM protein (p.Thr1885Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. 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: 127410). 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 disruptive, 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.

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