Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000455869 | SCV000538212 | uncertain significance | not specified | 2016-03-28 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Hu 2003 reported the R1459C variant in a family with AD segregation of pseudoxanthoma elasticum. Pomozi-2014 carried out functional studies and showed that in mouse hepatocytes the variant was active (suggesting polymorphism). However, this variant could not rescue the zebrafish phenotype (suggesting deleterious variant).1/15798 South Asian alleles in ExAC. |
| Labcorp Genetics |
RCV001851712 | SCV002140115 | uncertain significance | not provided | 2024-05-11 | 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 1459 of the ABCC6 protein (p.Arg1459Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of pseudoxanthoma elasticum (PMID: 12673275). ClinVar contains an entry for this variant (Variation ID: 6577). 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 ABCC6 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ABCC6 function (PMID: 24352041). 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. |
| Fulgent Genetics, |
RCV002482835 | SCV002779198 | uncertain significance | Autosomal recessive inherited pseudoxanthoma elasticum; Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of infancy, 2 | 2022-03-26 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000006955 | SCV000027151 | pathogenic | Autosomal recessive inherited pseudoxanthoma elasticum | 2004-05-01 | no assertion criteria provided | literature only |