Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000536410 | SCV000654238 | uncertain significance | Nemaline myopathy 8 | 2022-09-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 436 of the KLHL40 protein (p.Asp436Asn). This variant is present in population databases (rs372145157, gnomAD 0.05%). 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: 474327). 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. 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. |
Gene |
RCV001785659 | SCV002027738 | uncertain significance | not provided | 2021-11-11 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23746549) |
Ambry Genetics | RCV002525307 | SCV003696006 | uncertain significance | Inborn genetic diseases | 2024-11-14 | criteria provided, single submitter | clinical testing | The c.1306G>A (p.D436N) alteration is located in exon 2 (coding exon 2) of the KLHL40 gene. This alteration results from a G to A substitution at nucleotide position 1306, causing the aspartic acid (D) at amino acid position 436 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Mayo Clinic Laboratories, |
RCV001785659 | SCV005409183 | uncertain significance | not provided | 2024-05-16 | criteria provided, single submitter | clinical testing |