ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3358C>T (p.Arg1120Trp) (rs774951734)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561972 SCV000672474 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000810439 SCV000950638 uncertain significance Neuroblastoma 3 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1120 of the ALK protein (p.Arg1120Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs774951734, ExAC 0.01%). This variant has not been reported in the literature in individuals with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 485077). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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