ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.4193C>T (p.Pro1398Leu)

gnomAD frequency: 0.00014  dbSNP: rs531490912
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540490 SCV000648736 uncertain significance Neuroblastoma, susceptibility to, 3 2024-01-12 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 1398 of the ALK protein (p.Pro1398Leu). This variant is present in population databases (rs531490912, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. 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: 470866). 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.
Fulgent Genetics, Fulgent Genetics RCV000540490 SCV000897000 uncertain significance Neuroblastoma, susceptibility to, 3 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV003226944 SCV003923876 uncertain significance not provided 2022-11-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast or kidney cancer (Yehia et al., 2018); This variant is associated with the following publications: (PMID: 29684080)
Baylor Genetics RCV000540490 SCV004198645 uncertain significance Neuroblastoma, susceptibility to, 3 2023-09-28 criteria provided, single submitter clinical testing

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