Submissions for variant NM_004304.5(ALK):c.3260C>T (p.Thr1087Ile)

gnomAD frequency: 0.00001  dbSNP: rs113994090

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000020581	SCV000541896	uncertain significance	Neuroblastoma, susceptibility to, 3	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1087 of the ALK protein (p.Thr1087Ile). This variant is present in population databases (rs113994090, gnomAD 0.03%). This missense change has been observed in individual(s) with neuroblastoma (PMID: 18923524). ClinVar contains an entry for this variant (Variation ID: 21395). 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 disruptive. 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.
CeGaT Center for Human Genetics Tuebingen	RCV000997104	SCV001152219	uncertain significance	not provided	2018-04-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000997104	SCV002584474	uncertain significance	not provided	2023-06-21	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in a patient with neuroblastoma and in individuals with breast cancer in published literature (Chen et al., 2008; Shin et al., 2020); Published functional studies demonstrate neurite growth stimulation, cellular proliferation, and foci development similar to wild type (Chand et al., 2013); This variant is associated with the following publications: (PMID: 23201355, 21945349, 32019277, 18923524, 23104988, Qiu2022[article])
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153305	SCV003843554	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000020581	SCV004198522	uncertain significance	Neuroblastoma, susceptibility to, 3	2023-10-02	criteria provided, single submitter	clinical testing