Submissions for variant NM_001127178.3(PIGG):c.1956G>A (p.Trp652Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002472058	SCV002768422	pathogenic	Intellectual disability, autosomal recessive 53	2023-12-21	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy (MIM#616917). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other variants predicted to cause NMD comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1201 - Heterozygous variant detected in trans with a likely pathogenic heterozygous variant (NM_001127178.2(PIGG):c.641A>G; p.(His214Arg)) in a recessive disease. (SP) 1206 - This variant has been shown to be paternally inherited (by segregation analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
PreventionGenetics, part of Exact Sciences	RCV003418540	SCV004112959	likely pathogenic	PIGG-related disorder	2023-06-05	criteria provided, single submitter	clinical testing	The PIGG c.1956G>A variant is predicted to result in premature protein termination (p.Trp652*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in PIGG are expected to be pathogenic. This variant is interpreted as likely pathogenic.