ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.395A>G (p.Asn132Ser)

gnomAD frequency: 0.00001  dbSNP: rs767039942
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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 RCV000703080 SCV000831962 uncertain significance Nemaline myopathy 8 2021-03-10 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KLHL40-related disease. This variant is present in population databases (rs767039942, ExAC 0.006%). This sequence change replaces asparagine with serine at codon 132 of the KLHL40 protein (p.Asn132Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine.
Athena Diagnostics RCV001662775 SCV001880738 uncertain significance not provided 2020-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002536368 SCV003649244 uncertain significance Inborn genetic diseases 2022-10-25 criteria provided, single submitter clinical testing The c.395A>G (p.N132S) alteration is located in exon 1 (coding exon 1) of the KLHL40 gene. This alteration results from a A to G substitution at nucleotide position 395, causing the asparagine (N) at amino acid position 132 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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