ClinVar Miner

Submissions for variant NM_138459.5(NUS1):c.869G>A (p.Arg290His)

dbSNP: rs886037858
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000239673 SCV000950925 uncertain significance Congenital disorder of glycosylation, type IAA 2023-10-18 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 290 of the NUS1 protein (p.Arg290His). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with NUS1-related conditions (PMID: 25066056, 36672771). ClinVar contains an entry for this variant (Variation ID: 253197). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects NUS1 function (PMID: 25066056, 34532305). 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.
Institute of Human Genetics, University of Leipzig Medical Center RCV001253663 SCV001429500 uncertain significance Intellectual disability, autosomal dominant 55, with seizures 2018-02-06 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001262137 SCV001439902 pathogenic Congenital disorder of glycosylation 2019-01-01 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000239673 SCV002581702 likely pathogenic Congenital disorder of glycosylation, type IAA 2022-08-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701345 SCV005204195 likely pathogenic NUS1-related disorder 2024-06-20 criteria provided, single submitter clinical testing Variant summary: NUS1 c.869G>A (p.Arg290His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250746 control chromosomes (gnomAD). c.869G>A has been reported in the literature in multiple homozygous individuals affected with NUS1-Related Disorders (Park_2014, Halfmeyer_2022). These data indicate that the variant is likely to be associated with disease. Publications also reported experimental evidence demonstrating decreased enzyme function in patient derived cells (Park_2014), as well as in an in vitro expression system (Grabinska_2017). The following publications have been ascertained in the context of this evaluation (PMID: 25066056, 36672771, 28842490). ClinVar contains an entry for this variant (Variation ID: 253197). Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV000239673 SCV000297998 pathogenic Congenital disorder of glycosylation, type IAA 2021-10-20 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.