ClinVar Miner

Submissions for variant NM_133459.4(CCBE1):c.520T>C (p.Cys174Arg)

gnomAD frequency: 0.00002  dbSNP: rs121908254
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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 RCV001851511 SCV002281696 likely pathogenic not provided 2023-11-12 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 174 of the CCBE1 protein (p.Cys174Arg). This variant is present in population databases (rs121908254, gnomAD 0.004%). This missense change has been observed in individuals with Hennekam lymphangiectasia-lymphedema syndrome (PMID: 19935664, 23653581). ClinVar contains an entry for this variant (Variation ID: 450). 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). This variant disrupts the p.Cys174 amino acid residue in CCBE1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23653581, 26686525, 32472549). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 RCV000000479 SCV000020628 pathogenic Hennekam lymphangiectasia-lymphedema syndrome 1 2009-12-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000000479 SCV000091178 not provided Hennekam lymphangiectasia-lymphedema syndrome 1 no assertion provided not provided

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