Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000556186 | SCV000655407 | uncertain significance | Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency | 2021-05-04 | 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 disruptive, 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 JAGN1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 71 of the JAGN1 protein (p.Pro71Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. |