ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.100G>C (p.Asp34His)

gnomAD frequency: 0.00001  dbSNP: rs778565563
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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 RCV000793393 SCV000932742 uncertain significance Nemaline myopathy 8 2021-08-25 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed to segregate with nemaline myopathy in a family (PMID: 23746549). This variant is present in population databases (rs778565563, ExAC 0.002%). This sequence change replaces aspartic acid with histidine at codon 34 of the KLHL40 protein (p.Asp34His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000793393 SCV000992579 likely pathogenic Nemaline myopathy 8 2019-07-01 criteria provided, single submitter research ACMG codes: PS4M, PM1, PM2, PP3

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