ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7994C>T (p.Pro2665Leu)

dbSNP: rs1591184690
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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 RCV000812466 SCV000952780 uncertain significance Ataxia-telangiectasia syndrome 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2665 of the ATM protein (p.Pro2665Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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. 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.
Color Diagnostics, LLC DBA Color Health RCV001184410 SCV001350377 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-21 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 2665 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.
Ambry Genetics RCV001184410 SCV005176223 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-16 criteria provided, single submitter clinical testing The p.P2665L variant (also known as c.7994C>T), located in coding exon 53 of the ATM gene, results from a C to T substitution at nucleotide position 7994. The proline at codon 2665 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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