ClinVar Miner

Submissions for variant NM_018486.3(HDAC8):c.667C>T (p.Arg223Trp)

dbSNP: rs1556007534
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000761240 SCV000891196 likely pathogenic Cornelia de Lange syndrome 5 2017-04-11 criteria provided, single submitter clinical testing
GeneDx RCV001662805 SCV001872948 likely pathogenic not provided 2023-05-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25533962)
Labcorp Genetics (formerly Invitae), Labcorp RCV000761240 SCV004539589 uncertain significance Cornelia de Lange syndrome 5 2023-01-20 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 623138). 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. 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 HDAC8 protein function. This missense change has been observed in individual(s) with clinical features of Cornelia de Lange syndrome (PMID: 25533962). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 223 of the HDAC8 protein (p.Arg223Trp).

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