ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.1306G>A (p.Asp436Asn)

gnomAD frequency: 0.00006  dbSNP: rs372145157
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp 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.
GeneDx 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, Mayo Clinic RCV001785659 SCV005409183 uncertain significance not provided 2024-05-16 criteria provided, single submitter clinical testing

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