ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.976A>G (p.Ile326Val)

dbSNP: rs1555068422
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000528412 SCV000622890 uncertain significance Ataxia-telangiectasia syndrome 2022-07-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 326 of the ATM protein (p.Ile326Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ATM-related conditions (PMID: 31159747). ClinVar contains an entry for this variant (Variation ID: 453766). 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. 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.
GeneKor MSA RCV000708662 SCV000821883 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000708662 SCV001181126 likely benign Hereditary cancer-predisposing syndrome 2024-02-01 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Baylor Genetics RCV003470689 SCV004209509 uncertain significance Familial cancer of breast 2023-09-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV000528412 SCV001456873 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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