ClinVar Miner

Submissions for variant NM_017739.4(POMGNT1):c.1099C>T (p.Arg367Cys)

gnomAD frequency: 0.00005  dbSNP: rs36038536
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000648205 SCV000770019 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 2024-06-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 367 of the POMGNT1 protein (p.Arg367Cys). This variant is present in population databases (rs36038536, gnomAD 0.01%). This missense change has been observed in individual(s) with POMGNT1-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 538746). 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 POMGNT1 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg367 amino acid residue in POMGNT1. Other variant(s) that disrupt this residue have been observed in individuals with POMGNT1-related conditions (PMID: 17878207), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV001835049 SCV002089614 uncertain significance Muscle eye brain disease 2019-10-28 no assertion criteria provided clinical testing

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