ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3419A>G (p.Asn1140Ser)

dbSNP: rs2148169203
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001977068 SCV002270613 uncertain significance Neuroblastoma, susceptibility to, 3 2020-11-25 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with ALK-related conditions. This sequence change replaces asparagine with serine at codon 1140 of the ALK protein (p.Asn1140Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV005343241 SCV006012903 uncertain significance Hereditary cancer-predisposing syndrome 2025-01-28 criteria provided, single submitter clinical testing The p.N1140S variant (also known as c.3419A>G), located in coding exon 21 of the ALK gene, results from an A to G substitution at nucleotide position 3419. The asparagine at codon 1140 is replaced by serine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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