Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Lupski Lab, |
RCV000454164 | SCV000538007 | likely pathogenic | Abnormal brain morphology | criteria provided, single submitter | research | ||
Labcorp Genetics |
RCV001232846 | SCV001405418 | uncertain significance | Nephronophthisis 14 | 2019-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 1124 of the ZNF423 protein (p.Glu1124Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs548986682, ExAC 0.02%). This variant has been observed in individual(s) with neurologic disease (PMID: 26539891). ClinVar contains an entry for this variant (Variation ID: 402221). 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. 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. |