ClinVar Miner

Submissions for variant NM_001698.2(AUH):c.730G>A (p.Asp244Asn) (rs202182817)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000766066 SCV000897532 uncertain significance 3-Methylglutaconic aciduria type 1 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000195704 SCV000251178 uncertain significance not provided 2018-09-14 criteria provided, single submitter clinical testing p.Asp244Asn (GAT>AAT): c.730 G>A in exon 7 of the AUH gene (NM_001698.2). The D244N missense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is non-conservative as a negatively charged Aspartic Acid residue is replaced by an uncharged Asparagine residue. This change occurs at a position in the AUH protein that is conserved in mammals. A missense mutation at a nearby position (A240V) has been reported in association with 3-methylglutaconic aciduria type 1. In-silico analyses are not consistent in their predictions of whether or not D244N is damaging to the AUH protein. Therefore, based on the currently available information, it is unclear whether D244N is a disease-causing mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s).
Invitae RCV000766066 SCV000940696 uncertain significance 3-Methylglutaconic aciduria type 1 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 244 of the AUH protein (p.Asp244Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs202182817, ExAC 0.1%). This variant has not been reported in the literature in individuals with AUH-related disease. ClinVar contains an entry for this variant (Variation ID: 214146). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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