Submissions for variant NM_004304.5(ALK):c.2213G>T (p.Gly738Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003172191	SCV003859002	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-20	criteria provided, single submitter	clinical testing	The p.G738V variant (also known as c.2213G>T), located in coding exon 13 of the ALK gene, results from a G to T substitution at nucleotide position 2213. The glycine at codon 738 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003633688	SCV004446875	uncertain significance	Neuroblastoma, susceptibility to, 3	2023-03-22	criteria provided, single submitter	clinical testing	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. This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 738 of the ALK protein (p.Gly738Val).