ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.427C>T (p.Leu143Phe)

gnomAD frequency: 0.00001  dbSNP: rs780332509
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001769392 SCV002001262 uncertain significance not provided 2021-01-06 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001885049 SCV002137219 uncertain significance Nemaline myopathy 8 2022-07-08 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 143 of the KLHL40 protein (p.Leu143Phe). This variant is present in population databases (rs780332509, gnomAD 0.005%). 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: 1313746). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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 RCV004040276 SCV004892682 uncertain significance Inborn genetic diseases 2024-03-01 criteria provided, single submitter clinical testing The c.427C>T (p.L143F) alteration is located in exon 1 (coding exon 1) of the KLHL40 gene. This alteration results from a C to T substitution at nucleotide position 427, causing the leucine (L) at amino acid position 143 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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