Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV000415159 | SCV000328791 | uncertain significance | Hereditary coproporphyria | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001046689 | SCV001210603 | uncertain significance | not provided | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 447 of the CPOX protein (p.Arg447Cys). This variant is present in population databases (rs28931603, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of coproporphyria (PMID: 11309681, 12181641, 27959697, 33763395). ClinVar contains an entry for this variant (Variation ID: 459). 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 CPOX protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects CPOX function (PMID: 11309681). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Genetics and Molecular Pathology, |
RCV000415159 | SCV002761901 | uncertain significance | Hereditary coproporphyria | 2021-10-11 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001046689 | SCV004034761 | likely pathogenic | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | Reported with a second CPOX variant on the same allele (in cis) in affected individuals from three families with hereditary coproporphyria, as well as without a second CPOX variant in an unaffected individual from one of these families (Wiman et al., 2002); Published functional studies demonstrate significantly reduced CPOX enzyme activity (Lamoril et al., 2001); 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: 11309681, 27959697, 34426522, 31589614, 33763395, 12181641) |
Mayo Clinic Laboratories, |
RCV001046689 | SCV004226139 | uncertain significance | not provided | 2022-02-24 | criteria provided, single submitter | clinical testing | PP3, PS3 |
OMIM | RCV000000488 | SCV000020637 | pathogenic | Coproporphyria | 2002-01-01 | no assertion criteria provided | literature only |