ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.513C>T (p.Tyr171=)

dbSNP: rs786201693
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000988645 SCV001138437 likely pathogenic Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000988645 SCV003820772 likely pathogenic Ataxia-telangiectasia syndrome 2022-11-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000988645 SCV004296140 uncertain significance Ataxia-telangiectasia syndrome 2023-01-03 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with ataxia-telangiectasia (PMID: 14695534). ClinVar contains an entry for this variant (Variation ID: 802727). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 14695534). The resulting mRNA is expected to undergo nonsense-mediated decay. This sequence change affects codon 171 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. 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.
PreventionGenetics, part of Exact Sciences RCV004726758 SCV005338260 likely pathogenic ATM-related disorder 2024-08-27 no assertion criteria provided clinical testing The ATM c.513C>T variant is not predicted to result in an amino acid change (p.=). This variant has been reported as homozygous in an individual with ataxia telangiectasia (Table 1, Eng et al. 2004. PubMed ID: 14695534). Although this variant results in a silent protein change, it causes a splicing defect by activating a cryptic splice site that results in a premature termination codon (Eng et al. 2004. PubMed ID: 14695534). This variant has not been reported in a large population database, indicating this variant is rare. This variant has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from uncertain to likely pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/802727/). This variant is interpreted as likely pathogenic.

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