ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.1616C>T (p.Pro539Leu)

gnomAD frequency: 0.00001  dbSNP: rs780261738
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001313666 SCV001504170 uncertain significance Nemaline myopathy 8 2022-09-01 criteria provided, single submitter clinical testing 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1014870). This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. This variant is present in population databases (rs780261738, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 539 of the KLHL40 protein (p.Pro539Leu).
Ambry Genetics RCV002545062 SCV003709843 uncertain significance Inborn genetic diseases 2022-10-03 criteria provided, single submitter clinical testing The c.1616C>T (p.P539L) alteration is located in exon 5 (coding exon 5) of the KLHL40 gene. This alteration results from a C to T substitution at nucleotide position 1616, causing the proline (P) at amino acid position 539 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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