Submissions for variant NM_017739.4(POMGNT1):c.931C>T (p.Arg311Ter)

gnomAD frequency: 0.00001  dbSNP: rs386834039

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081807	SCV000113742	pathogenic	not provided	2013-06-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000081807	SCV000617417	pathogenic	not provided	2018-12-24	criteria provided, single submitter	clinical testing	The R311X variant in the POMGNT1 gene has been reported previously in two unrelated individuals with muscle eye brain disease, both of whom harbored a second POMGNT1 variant (Biancheri et al., 2006; Saredi et al., 2012). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R311X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R311X as a pathogenic variant.
Athena Diagnostics	RCV000081807	SCV001145193	pathogenic	not provided	2018-11-27	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001039421	SCV001202951	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3	2023-12-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg311*) in the POMGNT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMGNT1 are known to be pathogenic (PMID: 19299310, 20816175, 21447391, 26908613, 27391550). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with muscular dystrophy-dystroglycanopathy (PMID: 17030669, 22554691). ClinVar contains an entry for this variant (Variation ID: 56610). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003466920	SCV004206020	pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3	2022-09-06	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005016348	SCV005648450	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3; Retinitis pigmentosa 76	2024-05-17	criteria provided, single submitter	clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000050023	SCV000082432	probable-pathogenic	Muscle eye brain disease		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.
Counsyl	RCV000984204	SCV001132271	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2O	2015-04-02	no assertion criteria provided	clinical testing
Counsyl	RCV000984205	SCV001132272	likely pathogenic	Retinitis pigmentosa 76	2015-04-02	no assertion criteria provided	clinical testing
Counsyl	RCV000050023	SCV001132471	likely pathogenic	Muscle eye brain disease	2015-04-02	no assertion criteria provided	clinical testing
Counsyl	RCV000984300	SCV001132472	likely pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3	2015-04-02	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000050023	SCV001461195	pathogenic	Muscle eye brain disease	2020-09-16	no assertion criteria provided	clinical testing