ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3115G>A (p.Val1039Met) (rs200080181)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467803 SCV000541877 uncertain significance Neuroblastoma 3 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 1039 of the ALK protein (p.Val1039Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs200080181, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with ALK-related disease. ClinVar contains an entry for this variant (Variation ID: 404367). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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 RCV000467803 SCV001302252 uncertain significance Neuroblastoma 3 2017-04-28 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761097 SCV000891012 uncertain significance Retinoblastoma 2016-08-26 no assertion criteria provided clinical testing

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