Submissions for variant NM_014908.3(DOLK):c.1438A>G (p.Ile480Val) (rs144209926)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	RCV000431298	SCV000511615	uncertain significance	not provided	2016-06-30	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Invitae	RCV000808929	SCV000949062	uncertain significance	Congenital disorder of glycosylation type 1M	2018-08-23	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine with valine at codon 480 of the DOLK protein (p.Ile480Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs144209926, ExAC 0.03%). This variant has not been reported in the literature in individuals with DOLK-related disease. ClinVar contains an entry for this variant (Variation ID: 377266). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.