ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.413G>C (p.Arg138Pro)

gnomAD frequency: 0.00019  dbSNP: rs142285083
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000545599 SCV000654253 uncertain significance Nemaline myopathy 8 2022-08-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 138 of the KLHL40 protein (p.Arg138Pro). This variant is present in population databases (rs142285083, gnomAD 0.02%). 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: 474335). 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 disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV000545599 SCV002781957 uncertain significance Nemaline myopathy 8 2021-07-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV002525309 SCV003570380 uncertain significance Inborn genetic diseases 2021-12-03 criteria provided, single submitter clinical testing The c.413G>C (p.R138P) alteration is located in exon 1 (coding exon 1) of the KLHL40 gene. This alteration results from a G to C substitution at nucleotide position 413, causing the arginine (R) at amino acid position 138 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004592602 SCV005078396 uncertain significance not provided 2024-02-28 criteria provided, single submitter clinical testing Reported as a heterozygous variant in two patients with language impairment in the published literature (PMID: 28440294); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27149842, 28440294)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.