ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3594C>T (p.Leu1198=) (rs56071005)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226417 SCV000288347 benign Neuroblastoma 3 2018-01-11 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000324129 SCV000429931 likely benign Neuroblastoma Susceptibility 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000440731 SCV000519053 likely benign not specified 2018-01-30 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000440731 SCV000602468 benign not specified 2017-02-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563440 SCV000672460 likely benign Hereditary cancer-predisposing syndrome 2016-11-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Integrated Genetics/Laboratory Corporation of America RCV000440731 SCV000918418 benign not specified 2018-12-04 criteria provided, single submitter clinical testing Variant summary: ALK c.3594C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0014 in 276838 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is approximately 3355.03 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALK causing Neuroblastoma, Susceptibility Type 3 phenotype (4.2e-07), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3594C>T in individuals affected with Neuroblastoma, Susceptibility Type 3 and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000226417 SCV000734187 likely benign Neuroblastoma 3 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000226417 SCV000745625 benign Neuroblastoma 3 2015-12-23 no assertion criteria provided clinical testing

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