ClinVar Miner

Submissions for variant NM_133459.4(CCBE1):c.223T>A (p.Cys75Ser)

gnomAD frequency: 0.00007  dbSNP: rs121908250
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000434998 SCV000511567 pathogenic not provided 2016-06-20 criteria provided, single submitter clinical testing
GeneDx RCV000434998 SCV001782630 pathogenic not provided 2022-12-15 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with reduced ability to rescue zebrafish ccbe1 knockdown morphants (Alders et al., 2009); 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: 24167460, 19935664, 19911200, 34234628)
Labcorp Genetics (formerly Invitae), Labcorp RCV000434998 SCV002213183 pathogenic not provided 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 75 of the CCBE1 protein (p.Cys75Ser). This variant is present in population databases (rs121908250, gnomAD 0.02%). This missense change has been observed in individuals with clinical features of Hennekam lymphangiectasia-lymphedema syndrome (PMID: 19911200, 19935664, 22239599, 23653581, 24167460). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 445). 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 expected to disrupt CCBE1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CCBE1 function (PMID: 19935664). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000474 SCV000020623 pathogenic Hennekam lymphangiectasia-lymphedema syndrome 1 2010-02-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000000474 SCV000091175 not provided Hennekam lymphangiectasia-lymphedema syndrome 1 no assertion provided not provided

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