ClinVar Miner

Submissions for variant NM_004393.6(DAG1):c.1283G>A (p.Arg428Gln)

gnomAD frequency: 0.00004  dbSNP: rs780793711
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493077 SCV000581836 uncertain significance not provided 2017-04-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DAG1 gene. The R428Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R428Q variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R428Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. 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 RCV001071035 SCV001236317 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2P; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 428 of the DAG1 protein (p.Arg428Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs780793711, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with DAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 429305). 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 tolerated. 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 RCV000493077 SCV004234279 uncertain significance not provided 2023-05-03 criteria provided, single submitter clinical testing

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