Submissions for variant NM_006118.4(HAX1):c.358C>T (p.Arg120Trp)

gnomAD frequency: 0.00001  dbSNP: rs886045320

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000285455	SCV000348480	uncertain significance	Kostmann syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000285455	SCV003448540	uncertain significance	Kostmann syndrome	2021-08-30	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with tryptophan at codon 120 of the HAX1 protein (p.Arg120Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). 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: 292705). 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: "Possibly Damaging"; 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.
Ambry Genetics	RCV004975417	SCV005596145	uncertain significance	Inborn genetic diseases	2024-11-21	criteria provided, single submitter	clinical testing	The p.R120W variant (also known as c.358C>T), located in coding exon 3 of the HAX1 gene, results from a C to T substitution at nucleotide position 358. The arginine at codon 120 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.