ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3558A>T (p.Glu1186Asp)

dbSNP: rs12786957
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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 RCV000572499 SCV000672682 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-16 criteria provided, single submitter clinical testing The p.E1186D variant (also known as c.3558A>T), located in coding exon 23 of the ATM gene, results from an A to T substitution at nucleotide position 3558. The glutamic acid at codon 1186 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is well 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 RCV000572499 SCV001354052 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-26 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with aspartic acid at codon 1186 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 been detected in a breast cancer case-control meta-analysis in 2/60466 cases and 2/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID ATM_002255). This variant has been identified in 1/251328 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001312792 SCV001503263 uncertain significance Ataxia-telangiectasia syndrome 2022-07-08 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1186 of the ATM protein (p.Glu1186Asp). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 485209). 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.
Natera, Inc. RCV001312792 SCV002080529 uncertain significance Ataxia-telangiectasia syndrome 2021-09-21 no assertion criteria provided clinical testing

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