ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.210A>T (p.Lys70Asn)

gnomAD frequency: 0.00001  dbSNP: rs1064793030
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480401 SCV000564603 uncertain significance not specified 2014-11-06 criteria provided, single submitter clinical testing This variant is denoted ATM c.210A>T at the cDNA level, p.Lys70Asn (K70N) at the protein level, and results in the change of a Lysine to an Asparagine (AAA>AAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Lys70Asn 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 Lysine and Asparagine differ in some properties, this is considered a semi-conservative amino acid substitution. ATM Lys70Asn occurs at a position that is highly conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether ATM Lys70Asn is pathogenic or benign. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000551041 SCV000622307 uncertain significance Ataxia-telangiectasia syndrome 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 70 of the ATM protein (p.Lys70Asn). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 418022). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. 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.
Counsyl RCV000551041 SCV000800149 uncertain significance Ataxia-telangiectasia syndrome 2018-05-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002418494 SCV002725944 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-16 criteria provided, single submitter clinical testing The p.K70N variant (also known as c.210A>T), located in coding exon 3 of the ATM gene, results from an A to T substitution at nucleotide position 210. The lysine at codon 70 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV002418494 SCV004359516 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-31 criteria provided, single submitter clinical testing This missense variant replaces lysine with asparagine at codon 70 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31394 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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