Submissions for variant NM_001127178.3(PIGG):c.342dup (p.Thr115fs)

dbSNP: rs886041687

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000354375	SCV000330415	pathogenic	not provided	2024-10-01	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34113002)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001855069	SCV002229284	pathogenic	Intellectual disability, autosomal recessive 53	2023-04-09	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280494). This variant has not been reported in the literature in individuals affected with PIGG-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Thr115Tyrfs*50) in the PIGG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PIGG are known to be pathogenic (PMID: 26996948, 28581210, 28771251).
Baylor Genetics	RCV001855069	SCV003836383	likely pathogenic	Intellectual disability, autosomal recessive 53	2020-12-26	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000354375	SCV003839833	pathogenic	not provided	2022-07-22	no assertion criteria provided	clinical testing	DNA sequence analysis of the PIGG gene demonstrated a single base pair duplication in exon 2, c.342dup. This sequence change results in an amino acid frameshift and creates a premature stop codon 49 amino acids downstream of the change, p.Thr115Tyrfs*50. This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated PIGG protein with potentially abnormal function. This sequence change has been described in the gnomAD database in two individuals which corresponds to a population frequency of 0.005 % (dbSNP rs886041687). This sequence change has previously been described in an individual with developmental delay and intellectual disability with other PIGG deficiency–associated features along with another change in the same gene (PMID: 34113002). These collective evidences indicate that this sequence change is pathogenic, however functional studies have not been performed to prove this conclusively.