ClinVar Miner

Submissions for variant NM_017739.4(POMGNT1):c.286C>T (p.Arg96Trp)

gnomAD frequency: 0.00002  dbSNP: rs770834730
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000658410 SCV000335358 uncertain significance not provided 2015-10-06 criteria provided, single submitter clinical testing
GeneDx RCV000658410 SCV000780182 uncertain significance not provided 2018-05-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the POMGNT1 gene. The R96W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R96W variant is observed in 4/18870 (0.02%) alleles from individuals of East Asian background (Lek et al., 2016). The R96W variant 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001246342 SCV001419689 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 96 of the POMGNT1 protein (p.Arg96Trp). This variant is present in population databases (rs770834730, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 283338). 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 POMGNT1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Revvity Omics, Revvity RCV000658410 SCV003811759 uncertain significance not provided 2019-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV004021133 SCV005007233 uncertain significance Inborn genetic diseases 2024-02-05 criteria provided, single submitter clinical testing The c.286C>T (p.R96W) alteration is located in exon 4 (coding exon 3) of the POMGNT1 gene. This alteration results from a C to T substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001275756 SCV001461206 uncertain significance Muscle eye brain disease 2020-09-16 no assertion criteria provided clinical testing

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