ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.221C>T (p.Pro74Leu)

gnomAD frequency: 0.00001  dbSNP: rs1187464179
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000686168 SCV000813672 uncertain significance Neuroblastoma, susceptibility to, 3 2024-12-18 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 74 of the ALK protein (p.Pro74Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 566374). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Sema4, Sema4 RCV002257926 SCV002528418 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-07 criteria provided, single submitter curation
Ambry Genetics RCV002257926 SCV002729674 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-25 criteria provided, single submitter clinical testing The c.221C>T (p.P74L) alteration is located in exon 1 (coding exon 1) of the ALK gene. This alteration results from a C to T substitution at nucleotide position 221, causing the proline (P) at amino acid position 74 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000686168 SCV004197909 uncertain significance Neuroblastoma, susceptibility to, 3 2024-03-29 criteria provided, single submitter clinical testing
GeneDx RCV004773085 SCV005386650 uncertain significance not provided 2024-01-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.