ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3432G>A (p.Leu1144=)

gnomAD frequency: 0.00001  dbSNP: rs1060501625
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000476703 SCV000546919 pathogenic Ataxia-telangiectasia syndrome 2023-12-24 criteria provided, single submitter clinical testing This sequence change affects codon 1144 of the ATM mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATM protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of ataxia-telangiectasia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 407599). Studies have shown that this variant results in skipping of partial exon 24 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV001177305 SCV001341492 likely benign Hereditary cancer-predisposing syndrome 2019-02-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222514 SCV002500650 likely benign not specified 2022-03-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV001177305 SCV005038300 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-21 criteria provided, single submitter clinical testing The c.3432G>A variant (also known as p.L1144L), located in coding exon 23 of the ATM gene, results from a G to A substitution at nucleotide position 3432. This nucleotide substitution does not change the leucine at codon 1144. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004591303 SCV005080026 uncertain significance not provided 2023-08-31 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Myriad Genetics, Inc. RCV004591302 SCV005083138 benign Familial cancer of breast 2024-05-14 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Natera, Inc. RCV000476703 SCV002080407 uncertain significance Ataxia-telangiectasia syndrome 2021-09-16 no assertion criteria provided clinical testing

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