ClinVar Miner

Submissions for variant NM_017739.3(POMGNT1):c.1324C>T (p.Arg442Cys) (rs28940869)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000150001 SCV000843376 likely pathogenic not provided 2017-12-20 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000150001 SCV000281499 pathogenic not provided 2015-12-21 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000150001 SCV000331827 pathogenic not provided 2015-08-21 criteria provided, single submitter clinical testing
GeneDx RCV000150001 SCV000196861 pathogenic not provided 2017-05-11 criteria provided, single submitter clinical testing p.Arg442Cys (CGT>TGT): c.1324 C>T in exon 16 in the POMGNT1 gene (NM_017739.3). The R442C mutation in the POMGNT1 gene has been reported previously in mutiple individuals including 3 children with muscle-eye-brain disease (MEB), as well as two siblings with MEB and clinical features that included congenital hypotonia, global developmental delay, intellectual disability, early-onset glaucoma, and MRI findings characteristic of MEB (Hehr et al., 2007; Vervoort et al., 2004). Functional studies demonstrated complete loss of enzyme activity resulting from the R442C mutation in POMGNT1 (Voglmeir et al., 2011). The R442C mutation was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R442C mutation is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this mutation is probably damaging to the protein structure/function. Missense mutations at the same and a nearby residue (R442L, R442H, L440R) have been reported in association with muscle-eye-brain disease, supporting the functional importance of this region of the protein. We interpret R442C as a disease-causing mutation. The variant is found in POMGNT1 panel(s).
OMIM RCV000004199 SCV000024365 pathogenic Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A3 2004-07-01 no assertion criteria provided literature only

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