ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.78A>T (p.Glu26Asp) (rs786202953)

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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 RCV000166031 SCV000216791 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
GeneDx RCV000236303 SCV000293606 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing This variant is denoted ATM c.78A>T at the cDNA level, p.Glu26Asp (E26D) at the protein level, and results in the change of a Glutamic Acid to an Aspartic Acid (GAA>GAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Glu26Asp was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Glutamic Acid and Aspartic Acid share similar properties, this is considered a conservative amino acid substitution. ATM Glu26Asp occurs at a position that is conserved in mammals 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 evidence, it is unclear whether ATM Glu26Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000525440 SCV000622784 uncertain significance Ataxia-telangiectasia syndrome 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 26 of the ATM protein (p.Glu26Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. 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: 186439). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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