Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002031704 | SCV002312490 | uncertain significance | Nemaline myopathy 8 | 2021-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 240 of the KLHL40 protein (p.Arg240His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. 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. 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 | RCV003355790 | SCV004076402 | uncertain significance | Inborn genetic diseases | 2023-09-12 | criteria provided, single submitter | clinical testing | The c.719G>A (p.R240H) alteration is located in exon 1 (coding exon 1) of the KLHL40 gene. This alteration results from a G to A substitution at nucleotide position 719, causing the arginine (R) at amino acid position 240 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |