Submissions for variant NM_024989.4(PGAP1):c.331A>G (p.Lys111Glu)

gnomAD frequency: 0.00077  dbSNP: rs142320636

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000500227	SCV000596405	uncertain significance	not specified	2016-06-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705226	SCV000834213	uncertain significance	Intellectual disability, autosomal recessive 42	2022-09-23	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 111 of the PGAP1 protein (p.Lys111Glu). This variant is present in population databases (rs142320636, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PGAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 436297). 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 expected to disrupt PGAP1 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	RCV000997638	SCV001153258	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000705226	SCV001448968	uncertain significance	Intellectual disability, autosomal recessive 42	2019-11-18	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000705226	SCV001520817	uncertain significance	Intellectual disability, autosomal recessive 42	2019-01-15	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848874	SCV002105461	uncertain significance	Hereditary spastic paraplegia	2021-11-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000705226	SCV002783851	uncertain significance	Intellectual disability, autosomal recessive 42	2022-03-02	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000997638	SCV005188211	uncertain significance	not provided		criteria provided, single submitter	not provided
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000997638	SCV001979454	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000997638	SCV001980070	uncertain significance	not provided		no assertion criteria provided	clinical testing