ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5584C>T (p.Leu1862Phe)

dbSNP: rs149362482
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000709187 SCV000838555 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002256489 SCV002528565 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-16 criteria provided, single submitter curation
Invitae RCV000709187 SCV003217104 uncertain significance Ataxia-telangiectasia syndrome 2022-07-03 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. 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. ClinVar contains an entry for this variant (Variation ID: 584794). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is present in population databases (rs149362482, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1862 of the ATM protein (p.Leu1862Phe).
Color Diagnostics, LLC DBA Color Health RCV002256489 SCV004361753 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-21 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 1862 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 1/250984 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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