ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.602G>A (p.Trp201Ter)

gnomAD frequency: 0.00003  dbSNP: rs397509420
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000054414 SCV000654256 pathogenic Nemaline myopathy 8 2022-10-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 60516). This premature translational stop signal has been observed in individual(s) with severe congenital myopathy and fetal akinesia deformation sequence (PMID: 23746549, 27762439). This variant is present in population databases (rs397509420, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Trp201*) in the KLHL40 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KLHL40 are known to be pathogenic (PMID: 23746549).
GeneDx RCV000598839 SCV000709999 pathogenic not provided 2023-08-04 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27762439, 33060286, 35379254, 31908664, 23746549)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000598839 SCV002009677 pathogenic not provided 2021-11-03 criteria provided, single submitter clinical testing
OMIM RCV000054414 SCV000082891 pathogenic Nemaline myopathy 8 2013-07-11 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV004757124 SCV005363330 pathogenic KLHL40-related disorder 2024-06-26 no assertion criteria provided clinical testing The KLHL40 c.602G>A variant is predicted to result in premature protein termination (p.Trp201*). This variant has been reported, in the homozygous or heterozygous state, in at least two cases of severe nemaline myopathy or fetal akinesia deformation sequence (Family 7 in Ravenscroft et al. 2013. PubMed ID: 23746549; Chen et al. 2016. PubMed ID: 27762439). This variant is reported in 0.016% of alleles in individuals of South Asian descent in gnomAD. Nonsense variants in KLHL40 are expected to be pathogenic. This variant is interpreted as pathogenic.

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