ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.2452G>A (p.Gly818Arg) (rs777803249)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000706090 SCV000835122 uncertain significance Neuroblastoma 3 2019-11-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 818 of the ALK protein (p.Gly818Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs777803249, ExAC 0.001%). This variant has not been reported in the literature in individuals with ALK-related disease. 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 disruptive, but 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.
Illumina Clinical Services Laboratory,Illumina RCV000706090 SCV001299495 uncertain significance Neuroblastoma 3 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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