PIGV was first reported in relation to autosomal recessive hyperphosphatasia with intellectual disability syndrome 1 in 2010 (Krawitz et al., PMID: 20802478). 14 unique variants (13 missense, 1 nonsense) that have been reported in 18 probands in 8 publications (PMIDs: 20802478, 21739589, 22315194, 24129430, 27177984, 28688840, 28817240, 37863628) are included in this curation. One recurrent variant in the European population (NM_017837.4:c.1022C>A, p.Ala341Glu) has been observed in the homozygous state in 5 probands and in the compound heterozygous state in 9 probands. The mechanism of pathogenicity appears to be loss of function, although most variants reported in conjunction with this condition are missense variants without functional studies. This gene-disease relationship is also supported by a mouse knock-in model and a Chinese hamster ovary cell knockout model (PMIDs: 33402532, 22228761). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date June 18, 2025 (SOP Version 11).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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