ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5039C>T (p.Pro1680Leu)

gnomAD frequency: 0.00001  dbSNP: rs587782153
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130731 SCV000185622 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-18 criteria provided, single submitter clinical testing The p.P1680L variant (also known as c.5039C>T), located in coding exon 33 of the ATM gene, results from a C to T substitution at nucleotide position 5039. The proline at codon 1680 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000205355 SCV000260511 likely benign Ataxia-telangiectasia syndrome 2024-01-26 criteria provided, single submitter clinical testing
GeneDx RCV000481018 SCV000568012 uncertain significance not provided 2024-09-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast and/or ovarian cancer or with immunodeficiency (PMID: 28528518, 33471991, 34787773); This variant is associated with the following publications: (PMID: 31658756, 25303977, 33471991, 34787773, 33939675, 28528518)
Color Diagnostics, LLC DBA Color Health RCV000130731 SCV000682243 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-29 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 1680 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 been reported in two individuals affected with breast and/or ovarian cancer (PMID: 28528518, 33471991). This variant has been identified in 2/251186 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.
Counsyl RCV000205355 SCV000796964 uncertain significance Ataxia-telangiectasia syndrome 2018-01-05 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000130731 SCV002527812 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-07 criteria provided, single submitter curation
Baylor Genetics RCV003461998 SCV004206969 uncertain significance Familial cancer of breast 2024-02-29 criteria provided, single submitter clinical testing
Natera, Inc. RCV000205355 SCV002078406 uncertain significance Ataxia-telangiectasia syndrome 2020-01-22 no assertion criteria provided clinical testing

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