ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4397G>A (p.Arg1466Gln) (rs749770110)

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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 RCV000214216 SCV000272971 uncertain significance Hereditary cancer-predisposing syndrome 2014-11-11 criteria provided, single submitter clinical testing ​<span style="background-color: initial;">The<strong style="background-color: initial;"> p.R1466Q <span style="background-color: initial;">variant (also known as c.4397G>A), located in coding exon 28 of the <em style="background-color: initial;">ATM <span style="background-color: initial;">gene, results from a G to A substitution at nucleotide position 4397. The arginine at codon 1466 is replaced by glutamine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 22000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be benign and tolerated by PolyPhen and SIFT <em style="background-color: initial;">in silico <span style="background-color: initial;">analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.R1466Q remains unclear.
Color RCV000214216 SCV000682203 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-15 criteria provided, single submitter clinical testing
Invitae RCV000705795 SCV000834810 uncertain significance Ataxia-telangiectasia syndrome 2019-10-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1466 of the ATM protein (p.Arg1466Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs749770110, ExAC 0.009%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 229676). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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.
Natera, Inc. RCV000705795 SCV001462323 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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