Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000694750 | SCV000823208 | uncertain significance | DPAGT1-congenital disorder of glycosylation; Congenital myasthenic syndrome 13 | 2022-08-15 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. Experimental studies have shown that this missense change affects DPAGT1 function (PMID: 12872255). ClinVar contains an entry for this variant (Variation ID: 12296). This variant is also known as c.660A>G. This missense change has been observed in individual(s) with congenital disorder of glycosylation 1J (CDG-Ij) (PMID: 12872255, 30117111). This variant is present in population databases (rs28934876, gnomAD 0.004%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 170 of the DPAGT1 protein (p.Tyr170Cys). |
Gene |
RCV001567586 | SCV001791299 | likely pathogenic | not provided | 2021-01-21 | criteria provided, single submitter | clinical testing | Identified in trans with another DPAGT1 missense variant, p.A195G, in two siblings with abnormal neurological findings, with one sibling reported to have abnormal transferrin studies consistent with a type 1 congenital disorder of glycosylation (Kane et al., 2016; Ng et al., 2019); Published functional studies demonstrate a damaging effect: reduced N-acetyl-glucosamine-1 phosphate transferase (GPT) activity in in vitro assays (Wu et al., 2003); Identified in a patient with congenital disorder of glycosylation type 1j who reportedly harbored a second unknown variant in trans which resulted in decreased mRNA levels (Wu et al., 2003); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 30117111, 12872255, 26805780, 31519321, 30388443, 22304930, 23249953, 22742743) |
OMIM | RCV000013090 | SCV000033336 | pathogenic | DPAGT1-congenital disorder of glycosylation | 2003-08-01 | no assertion criteria provided | literature only | |
University of Washington Center for Mendelian Genomics, |
RCV001291042 | SCV001479374 | likely pathogenic | Congenital disorder of glycosylation | no assertion criteria provided | research |