Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000700418 | SCV000829172 | uncertain significance | Nemaline myopathy 8 | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 532 of the KLHL40 protein (p.Ile532Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs368161576, ExAC 0.005%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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. |
Prevention |
RCV003907953 | SCV004733006 | uncertain significance | KLHL40-related disorder | 2024-02-08 | no assertion criteria provided | clinical testing | The KLHL40 c.1595T>C variant is predicted to result in the amino acid substitution p.Ile532Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0086% of alleles in individuals of European (non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |