ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.1043C>A (p.Ala348Asp)

gnomAD frequency: 0.00001  dbSNP: rs760596486
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000813127 SCV000953469 uncertain significance Neuroblastoma, susceptibility to, 3 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 348 of the ALK protein (p.Ala348Asp). This variant is present in population databases (rs760596486, gnomAD 0.002%). 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: 656656). 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 tolerated. 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.
GeneDx RCV003324798 SCV004030655 uncertain significance not provided 2023-08-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies demonstrate sensitivity to ALK kinase inhibitors (Maxson et al., 2015); This variant is associated with the following publications: (PMID: 33198314, 26032424)

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