ClinVar Miner

Submissions for variant NM_152393.4(KLHL40):c.1405G>T (p.Gly469Cys)

dbSNP: rs367579275
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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 RCV000054411 SCV002304880 likely pathogenic Nemaline myopathy 8 2021-06-25 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 469 of the KLHL40 protein (p.Gly469Cys). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with nemaline myopathy (PMID: 23746549, 25721947). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 60513). 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"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000054411 SCV000082888 pathogenic Nemaline myopathy 8 2013-07-11 no assertion criteria provided literature only

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