ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.4210C>T (p.Leu1404Phe)

dbSNP: rs757615099
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000696766 SCV000825343 uncertain significance Neuroblastoma, susceptibility to, 3 2022-06-08 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 574752). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs757615099, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1404 of the ALK protein (p.Leu1404Phe).
Ambry Genetics RCV002332461 SCV002629498 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-02 criteria provided, single submitter clinical testing The p.L1404F variant (also known as c.4210C>T), located in coding exon 29 of the ALK gene, results from a C to T substitution at nucleotide position 4210. The leucine at codon 1404 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
GeneDx RCV003442038 SCV004169944 uncertain significance not provided 2023-05-09 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; This variant is associated with the following publications: (PMID: 30216592)

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