ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1835T>C (p.Leu612Pro)

dbSNP: rs1555072474
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000547363 SCV000622287 uncertain significance Ataxia-telangiectasia syndrome 2019-11-08 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 453388). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 612 of the ATM protein (p.Leu612Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.
Color Diagnostics, LLC DBA Color Health RCV001524423 SCV001734253 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-15 criteria provided, single submitter clinical testing This missense variant replaces leucine with proline at codon 612 of the ATM protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 not been identified 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.
GeneDx RCV001770401 SCV002002421 uncertain significance not provided 2020-07-08 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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