ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.50A>G (p.His17Arg)

dbSNP: rs1242444722
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001181264 SCV001346365 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-22 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 17 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 ATM-related disorders in the literature. This variant has been identified in 1/251394 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 RCV001278349 SCV002248887 uncertain significance Ataxia-telangiectasia syndrome 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 17 of the ATM protein (p.His17Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). 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: 921708). 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.
Ambry Genetics RCV001181264 SCV002641931 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-21 criteria provided, single submitter clinical testing The p.H17R variant (also known as c.50A>G), located in coding exon 1 of the ATM gene, results from an A to G substitution at nucleotide position 50. The histidine at codon 17 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Baylor Genetics RCV004570356 SCV005055943 uncertain significance Familial cancer of breast 2024-03-17 criteria provided, single submitter clinical testing
Natera, Inc. RCV001278349 SCV001465354 uncertain significance Ataxia-telangiectasia syndrome 2020-04-11 no assertion criteria provided clinical testing

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