Submissions for variant NM_032634.4(PIGO):c.1132C>T (p.Leu378Phe)

gnomAD frequency: 0.00016  dbSNP: rs746870615

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000999156	SCV000491003	uncertain significance	not provided	2024-11-03	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 38044714, 37656370)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000693432	SCV000821301	uncertain significance	Hyperphosphatasia with intellectual disability syndrome 2	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 378 of the PIGO protein (p.Leu378Phe). This variant is present in population databases (rs746870615, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PIGO-related conditions. ClinVar contains an entry for this variant (Variation ID: 372633). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PIGO protein function. 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.
CeGaT Center for Human Genetics Tuebingen	RCV000999156	SCV001155634	uncertain significance	not provided	2019-04-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002524638	SCV003682828	uncertain significance	Inborn genetic diseases	2021-10-29	criteria provided, single submitter	clinical testing	The c.1132C>T (p.L378F) alteration is located in exon 7 (coding exon 6) of the PIGO gene. This alteration results from a C to T substitution at nucleotide position 1132, causing the leucine (L) at amino acid position 378 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000693432	SCV003808351	uncertain significance	Hyperphosphatasia with intellectual disability syndrome 2	2019-04-19	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000999156	SCV001799284	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000999156	SCV001952662	uncertain significance	not provided		no assertion criteria provided	clinical testing