ClinVar Miner

Submissions for variant NM_006118.4(HAX1):c.461C>T (p.Pro154Leu)

gnomAD frequency: 0.00001  dbSNP: rs1389861333
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001047979 SCV001211966 uncertain significance Kostmann syndrome 2019-11-21 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with HAX1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 154 of the HAX1 protein (p.Pro154Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine.
Ambry Genetics RCV004986760 SCV005596151 uncertain significance Inborn genetic diseases 2024-11-22 criteria provided, single submitter clinical testing The p.P154L variant (also known as c.461C>T), located in coding exon 3 of the HAX1 gene, results from a C to T substitution at nucleotide position 461. The proline at codon 154 is replaced by leucine, an amino acid with similar 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.
Natera, Inc. RCV001047979 SCV001455155 uncertain significance Kostmann syndrome 2020-01-24 no assertion criteria provided clinical testing

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