ClinVar Miner

Submissions for variant NM_001382.4(DPAGT1):c.509A>G (p.Tyr170Cys)

gnomAD frequency: 0.00002  dbSNP: rs28934876
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Total submissions: 4
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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).
GeneDx 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, University of Washington RCV001291042 SCV001479374 likely pathogenic Congenital disorder of glycosylation no assertion criteria provided research

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