Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001753490 | SCV001986376 | uncertain significance | not provided | 2019-01-09 | criteria provided, single submitter | clinical testing | Identified in heterozygous state in a patient with hypoaldosteronism referred for genetic testing at GeneDx and in published literature in unrelated individuals with pseudohypoaldosteronism type II (Boyden et al., 2012; Glover et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Functional studies demonstrated that A340V shows binding to Cullin 3 and WNK1 that is similar to wild type KLHL3 protein (Ohta et al., 2013); This variant is associated with the following publications: (PMID: 22266938, 23387299, 24641320, 24266877) |
| Fulgent Genetics, |
RCV002477256 | SCV002778168 | uncertain significance | Pseudohypoaldosteronism type 2D | 2024-04-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001753490 | SCV004292860 | uncertain significance | not provided | 2023-01-25 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change does not substantially affect KLHL3 function (PMID: 23387299). ClinVar contains an entry for this variant (Variation ID: 100530). This missense change has been observed in individual(s) with autosomal dominant Gordon's syndrome (PMID: 22266938). This variant is present in population databases (rs199469628, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 340 of the KLHL3 protein (p.Ala340Val). |
| Richard Lifton Laboratory, |
RCV000128502 | SCV000119152 | pathogenic | Pseudohypoaldosteronism type 2A | no assertion criteria provided | not provided | Converted during submission to Pathogenic. |