ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.931C>A (p.Arg311Ser) (rs763283033)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541547 SCV000654261 uncertain significance Nemaline myopathy 8 2016-11-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 311 of the KLHL40 protein (p.Arg311Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is present in population databases (rs763283033, ExAC 0.03%). This variant has been reported in the homozygous state in an individual affected with nemaline myopathy (PMID: 26578207). A different missense substitution at this codon (p.Arg311Leu) has been reported in an individual affected with nemaline myopathy (PMID: 23746549). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Diagnostics Division,Centre for DNA Fingerprinting and Diagnostics RCV000541547 SCV000864074 likely pathogenic Nemaline myopathy 8 2017-01-01 criteria provided, single submitter research

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