ClinVar Miner

Submissions for variant NM_017739.4(POMGNT1):c.1490G>A (p.Arg497Gln)

gnomAD frequency: 0.00001  dbSNP: rs573518562
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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) RCV000153761 SCV000203335 uncertain significance not provided 2014-03-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000622475 SCV000741945 likely pathogenic Inborn genetic diseases 2016-11-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002516092 SCV003522662 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 497 of the POMGNT1 protein (p.Arg497Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs573518562, ExAC 0.001%). This missense change has been observed in individual(s) with clinical features of ventriculomegaly (PMID: 29096039). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 167526). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV002516093 SCV003761160 uncertain significance Muscular dystrophy-dystroglycanopathy 2023-01-24 criteria provided, single submitter curation The p.Arg497Gln variant in POMGNT1 has been previously reported in the literature in one individual, in the homozygous state, with POMGNT1-associated muscular dystrophy-dystroglycanopathy (PMID: 29096039), and has been identified in 0.007% (2/30614) South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs573518562). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#:167526) as likely pathogenic by Ambry Genetics and as a variant of uncertain significance by Eurofins NTD LLC (GA). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg497Gln variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PM3_Supporting, PP3 (Richards 2015).
Dept Of Ophthalmology, Nagoya University RCV003888594 SCV004708040 uncertain significance Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Fulgent Genetics, Fulgent Genetics RCV005025233 SCV005655800 likely 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 2024-04-10 criteria provided, single submitter clinical testing

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