ClinVar Miner

Submissions for variant NM_003859.2(DPM1):c.455G>T (p.Gly152Val) (rs587777116)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000087036 SCV000639038 pathogenic Congenital disorder of glycosylation type 1E 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 152 of the DPM1 protein (p.Gly152Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in individuals affected with congenital disorder of glycosylation type 1 (PMID: 23856421, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 100636). Experimental studies have shown that this missense change results in a large reduction in activity of the protein encoded by DPM1 activity in fibroblasts from an individual with a second pathogenic DPM1 variant and reduced binding of the protein, in vitro, to DPM3 which is another subunit of the dolichyl-phosphate mannosyltransferase complex (PMID: 23856421). Zebrafish studies have also shown this variant abolishes DPM1 protein function in-vivo (PMID: 26729507). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000087036 SCV000119850 pathogenic Congenital disorder of glycosylation type 1E 2013-11-01 no assertion criteria provided literature only

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