ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1834C>T (p.Leu612Phe)

dbSNP: rs747242300
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000539435 SCV000622286 uncertain significance Ataxia-telangiectasia syndrome 2024-01-05 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 612 of the ATM protein (p.Leu612Phe). This variant is present in population databases (rs747242300, gnomAD 0.01%). 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: 453387). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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 RCV001182000 SCV001347305 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-01 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 612 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 4/250820 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.
Sema4, Sema4 RCV001182000 SCV002533397 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-24 criteria provided, single submitter curation
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV002463718 SCV002601578 uncertain significance Familial cancer of breast 2022-10-04 criteria provided, single submitter clinical testing A heterozygous missense variation in exon 12 of the ATM gene (chr11:g.108252848C>T; Depth: 85x) that results in the amino acid substitution of Phenylalanine for Leucine at codon 612 (p.Leu612Phe; ENST00000675843.1) was detected (Table). The observed variation is documented as variant of uncertain significance in hereditary cancer-predisposing syndrome in the ClinVar database [VCV000453387.4]. The p.Leu612Phe variant has not been reported in the 1000 genomes and gnomAD databases and has a minor allele frequency of 0.01% in the our internal database. The in silico predictions# of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and Mutation Taster2 tools. The reference codon is conserved across species.
Ambry Genetics RCV001182000 SCV002716967 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-19 criteria provided, single submitter clinical testing The p.L612F variant (also known as c.1834C>T), located in coding exon 11 of the ATM gene, results from a C to T substitution at nucleotide position 1834. The leucine at codon 612 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV002463718 SCV004208812 uncertain significance Familial cancer of breast 2023-10-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV000539435 SCV001461085 uncertain significance Ataxia-telangiectasia syndrome 2020-04-16 no assertion criteria provided clinical testing

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