Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000688815 | SCV000816439 | uncertain significance | Nemaline myopathy 8 | 2022-09-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 598 of the KLHL40 protein (p.Arg598Gln). This variant is present in population databases (rs775821505, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. ClinVar contains an entry for this variant (Variation ID: 568454). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KLHL40 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Ambry Genetics | RCV004026305 | SCV004892680 | uncertain significance | Inborn genetic diseases | 2024-01-04 | criteria provided, single submitter | clinical testing | The c.1793G>A (p.R598Q) alteration is located in exon 6 (coding exon 6) of the KLHL40 gene. This alteration results from a G to A substitution at nucleotide position 1793, causing the arginine (R) at amino acid position 598 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |