Submissions for variant NM_153682.3(PIGP):c.384del (p.Glu129fs)

dbSNP: rs778481061

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000496365	SCV001150211	pathogenic	Developmental and epileptic encephalopathy, 55	2018-10-11	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001543513	SCV001762128	pathogenic	not provided	2021-06-17	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000496365	SCV002024631	likely pathogenic	Developmental and epileptic encephalopathy, 55	2021-01-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001543513	SCV002246996	pathogenic	not provided	2024-10-15	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the PIGP gene (p.Glu153Asnfs*34). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acid(s) of the PIGP protein and extend the protein by 27 additional amino acid residues. This variant is present in population databases (rs778481061, gnomAD 0.007%). This frameshift has been observed in individual(s) with developmental and epileptic encephalopathy (PMID: 28334793, 31139695, 32042915). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as c.384del. ClinVar contains an entry for this variant (Variation ID: 397552). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this frameshift affects PIGP function (PMID: 28334793). For these reasons, this variant has been classified as Pathogenic.
DASA	RCV000496365	SCV002567983	pathogenic	Developmental and epileptic encephalopathy, 55	2022-08-10	criteria provided, single submitter	clinical testing	The c.384del;p.(Glu129Asnfs*34) is a null frameshift variant (NMD) in the PIGP gene without sufficient information about prediction of nonsense mediated mRNA decay (NMD); it is present in a relevant exon to the transcript, and disrupts < 10% of the protein product – PVS1_moderate. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant(ClinVar ID: ID: 397552; OMIM: 605938.0002; PMID: 32042915; 31139695; 28334793) - PS4. The variant is present at low allele frequencies population databases (rs778481061 – gnomAD 0.0003944%; ABraOM no frequency - https://abraom.ib.usp.br/) -PM2_supporting.The p.(Glu129Asnfs*34) was detected in trans with a pathogenic variant (PMID: 32042915; 31139695; 28334793) - PM3_strong. The variant co-segregated with disease in multiple affected family members (PMID: 32042915) - PP1_moderate. In summary, the currently available evidence indicates that the variant is pathogenic.
Care4Rare-SOLVE, CHEO	RCV000449561	SCV000537759	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2017-02-23	no assertion criteria provided	research	This variant was found in a compound heterozygous state with c.74T>C.
OMIM	RCV000496365	SCV000586814	pathogenic	Developmental and epileptic encephalopathy, 55	2020-11-11	no assertion criteria provided	literature only