Submissions for variant NM_001127178.3(PIGG):c.768_769dup (p.Thr257fs)

dbSNP: rs1229339759

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001382316	SCV001580999	pathogenic	Intellectual disability, autosomal recessive 53	2020-04-14	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with PIGG-related conditions. Loss-of-function variants in PIGG are known to be pathogenic (PMID: 26996948, 28581210, 28771251). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr257Argfs*30) in the PIGG gene. It is expected to result in an absent or disrupted protein product.
Neuberg Centre For Genomic Medicine, NCGM	RCV001382316	SCV004047694	likely pathogenic	Intellectual disability, autosomal recessive 53		criteria provided, single submitter	clinical testing	The frameshift variant c.768_769dup (p.Thr257ArgfsTer30) in PIGG gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Pathogenic. The p.Thr257ArgfsTer30 variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.02229% is reported in gnomAD. This variant causes a frameshift starting with codon Threonine 257, changes this amino acid to Arginine residue, and creates a premature Stop codon at position 30 of the new reading frame, denoted p.Thr257ArgfsTer30. This variant is predicted to cause loss of normal protein function. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.