Submissions for variant NM_001382.4(DPAGT1):c.125G>A (p.Cys42Tyr)

gnomAD frequency: 0.00029  dbSNP: rs375679649

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000327645	SCV000367726	uncertain significance	DPAGT1-congenital disorder of glycosylation	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000444450	SCV000510915	uncertain significance	not provided	2016-09-22	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Athena Diagnostics Inc	RCV000517176	SCV000613164	uncertain significance	not specified	2016-09-07	criteria provided, single submitter	clinical testing
Invitae	RCV000529305	SCV000652718	uncertain significance	DPAGT1-congenital disorder of glycosylation; Congenital myasthenic syndrome 13	2022-08-23	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 42 of the DPAGT1 protein (p.Cys42Tyr). This variant is present in population databases (rs375679649, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with DPAGT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 302751). 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. 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.
Fulgent Genetics, Fulgent Genetics	RCV000529305	SCV002776391	uncertain significance	DPAGT1-congenital disorder of glycosylation; Congenital myasthenic syndrome 13	2021-10-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003278753	SCV003958338	uncertain significance	Inborn genetic diseases	2023-05-24	criteria provided, single submitter	clinical testing	The c.125G>A (p.C42Y) alteration is located in exon 1 (coding exon 1) of the DPAGT1 gene. This alteration results from a G to A substitution at nucleotide position 125, causing the cysteine (C) at amino acid position 42 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.