Submissions for variant NM_004304.5(ALK):c.3271G>A (p.Asp1091Asn)

gnomAD frequency: 0.00001  dbSNP: rs864309584

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202983	SCV000257950	uncertain significance	not specified	2015-06-18	criteria provided, single submitter	clinical testing
Invitae	RCV000647422	SCV000769218	uncertain significance	Neuroblastoma, susceptibility to, 3	2024-01-06	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1091 of the ALK protein (p.Asp1091Asn). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 218628). 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. Experimental studies have shown that this missense change does not substantially affect ALK function (PMID: 23104988). 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000761080	SCV000890995	uncertain significance	Familial isolated pituitary adenoma	2021-05-20	criteria provided, single submitter	clinical testing
Database of Curated Mutations (DoCM)	RCV000420164	SCV000503785	pathogenic	Neuroblastoma	2014-10-02	no assertion criteria provided	literature only