Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001061938 | SCV001226702 | uncertain significance | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 | 2019-03-14 | 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C65". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 NCF4-related conditions. This variant is present in population databases (rs752651381, ExAC 0.01%). This sequence change replaces tyrosine with cysteine at codon 348 of the NCF4 protein (p.Tyr348Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. |