ClinVar Miner

Submissions for variant NM_006118.4(HAX1):c.829C>T (p.Arg277Trp)

gnomAD frequency: 0.00018  dbSNP: rs138296453
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000653742 SCV000775632 uncertain significance Kostmann syndrome 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 277 of the HAX1 protein (p.Arg277Trp). This variant is present in population databases (rs138296453, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with HAX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 543083). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics, Fulgent Genetics RCV000653742 SCV000896156 uncertain significance Kostmann syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001570508 SCV001794812 uncertain significance not provided 2023-10-12 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003163009 SCV003884096 uncertain significance Inborn genetic diseases 2024-11-22 criteria provided, single submitter clinical testing The p.R277W variant (also known as c.829C>T), located in coding exon 7 of the HAX1 gene, results from a C to T substitution at nucleotide position 829. The arginine at codon 277 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Natera, Inc. RCV000653742 SCV001455158 uncertain significance Kostmann syndrome 2020-01-08 no assertion criteria provided clinical testing

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.