ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.590C>A (p.Ala197Glu)

gnomAD frequency: 0.00004  dbSNP: rs757677971
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001863905 SCV002125944 uncertain significance Nemaline myopathy 8 2021-10-08 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 197 of the KLHL40 protein (p.Ala197Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is present in population databases (rs757677971, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. 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 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.
Ambry Genetics RCV003164088 SCV003876276 uncertain significance Inborn genetic diseases 2023-02-14 criteria provided, single submitter clinical testing The c.590C>A (p.A197E) alteration is located in exon 1 (coding exon 1) of the KLHL40 gene. This alteration results from a C to A substitution at nucleotide position 590, causing the alanine (A) at amino acid position 197 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.