ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3460G>A (p.Glu1154Lys)

dbSNP: rs1005846150
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817475 SCV000958038 uncertain significance Neuroblastoma, susceptibility to, 3 2023-12-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1154 of the ALK protein (p.Glu1154Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 660309). 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.
Ambry Genetics RCV003380749 SCV004092499 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-14 criteria provided, single submitter clinical testing The p.E1154K variant (also known as c.3460G>A), located in coding exon 22 of the ALK gene, results from a G to A substitution at nucleotide position 3460. The glutamic acid at codon 1154 is replaced by lysine, an amino acid with 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.
GeneDx RCV004777896 SCV005390839 uncertain significance not provided 2024-04-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31585938, 31446141, 38448512)

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