ClinVar Miner

Submissions for variant NM_017739.4(POMGNT1):c.251G>A (p.Arg84His)

dbSNP: rs373866304
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521285 SCV000619798 uncertain significance not provided 2017-08-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the POMGNT1 gene. The R84H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R84H variant is observed in 5/10388 (0.05%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R84H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. 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 RCV000540487 SCV000649964 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 84 of the POMGNT1 protein (p.Arg84His). This variant is present in population databases (rs373866304, gnomAD 0.04%). 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: 451139). 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. 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.
CeGaT Center for Human Genetics Tuebingen RCV000521285 SCV004123781 likely benign not provided 2022-05-01 criteria provided, single submitter clinical testing POMGNT1: BP4
Ambry Genetics RCV004659083 SCV005149027 uncertain significance Inborn genetic diseases 2024-03-28 criteria provided, single submitter clinical testing The c.251G>A (p.R84H) alteration is located in exon 4 (coding exon 3) of the POMGNT1 gene. This alteration results from a G to A substitution at nucleotide position 251, causing the arginine (R) at amino acid position 84 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001829507 SCV002090237 uncertain significance Muscle eye brain disease 2020-07-28 no assertion criteria provided clinical testing

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