Submissions for variant NM_004304.5(ALK):c.864G>C (p.Trp288Cys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003816064	SCV004612303	uncertain significance	Neuroblastoma, susceptibility to, 3	2023-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 288 of the ALK protein (p.Trp288Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALK-related conditions. 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. 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.
Ambry Genetics	RCV004634357	SCV005120987	uncertain significance	Hereditary cancer-predisposing syndrome	2024-04-05	criteria provided, single submitter	clinical testing	The p.W288C variant (also known as c.864G>C), located in coding exon 3 of the ALK gene, results from a G to C substitution at nucleotide position 864. The tryptophan at codon 288 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.