Submissions for variant NM_001127178.3(PIGG):c.2843G>A (p.Trp948Ter)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005207943	SCV005844495	uncertain significance	Intellectual disability, autosomal recessive 53	2025-02-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp948*) in the PIGG gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 36 amino acid(s) of the PIGG protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PIGG-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the PIGG protein in which other variant(s) (p.Tyr957*) have been observed in individuals with PIGG-related conditions (PMID: 34113002). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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.