ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.1709C>T (p.Thr570Met)

gnomAD frequency: 0.00016  dbSNP: rs139268932
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000651590 SCV000773444 uncertain significance Nemaline myopathy 8 2022-09-12 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 570 of the KLHL40 protein (p.Thr570Met). This variant is present in population databases (rs139268932, gnomAD 0.03%). 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: 541331). 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.
Baylor Genetics RCV000651590 SCV001528627 uncertain significance Nemaline myopathy 8 2018-12-23 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001584504 SCV001817983 uncertain significance not provided 2019-12-05 criteria provided, single submitter clinical testing 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

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