ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7841C>A (p.Pro2614His)

dbSNP: rs769207177
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573170 SCV000660720 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-29 criteria provided, single submitter clinical testing The p.P2614H variant (also known as c.7841C>A), located in coding exon 52 of the ATM gene, results from a C to A substitution at nucleotide position 7841. The proline at codon 2614 is replaced by histidine, an amino acid with similar properties. A different alteration at this position, p.P2614S, has been detected in 1/4112 breast cancer patients and 0/2399 healthy control individuals across numerous studies (Tavtigian S et al. Am J Hum Genet. 2009 Oct;85(4):427-46). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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 RCV001061732 SCV001226485 uncertain significance Ataxia-telangiectasia syndrome 2022-07-16 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 2614 of the ATM protein (p.Pro2614His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 479057). 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 tolerated. 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.
Baylor Genetics RCV004569093 SCV005053024 uncertain significance Familial cancer of breast 2023-11-17 criteria provided, single submitter clinical testing

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