ClinVar Miner

Submissions for variant NM_000096.4(CP):c.188T>C (p.Ile63Thr)

gnomAD frequency: 0.00001  dbSNP: rs759185877
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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 RCV002025697 SCV002291443 uncertain significance Deficiency of ferroxidase 2022-09-03 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 63 of the CP protein (p.Ile63Thr). This variant is present in population databases (rs759185877, gnomAD 0.003%). This missense change has been observed in individual(s) with CP-related conditions (PMID: 15557511). ClinVar contains an entry for this variant (Variation ID: 1503773). 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 CP protein function. Experimental studies have shown that this missense change affects CP function (PMID: 16150804). 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.
GeneDx RCV002511125 SCV002820659 likely pathogenic not provided 2022-07-07 criteria provided, single submitter clinical testing Identified in the heterozygous state in a patient with Parkinson's disease in the published literature (Hochstrasser et al., 2004); Published functional studies demonstrate a damaging effect on N-glycosylation leading to ER accumulation and untranslated protein response (Hochstrasser et al., 2005); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 16755382, 16150804, 15557511)

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