Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000254915 | SCV000321369 | pathogenic | not provided | 2022-07-26 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect with R1314W resulting in abnormal protein trafficking and inappropriate intracellular accumulation (Le Saux et al., 2011); 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: 16392638, 22209248, 10835642, 30537162, 34205333, 34906475, 21935449, 24008425, 19339160, 24352041, 23483032, 27994049, 28102862, 28416300, 27826008, 32445016, 31589614, 34440381, 33005041, 32873932) |
| Labcorp Genetics |
RCV000254915 | SCV001587439 | pathogenic | not provided | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1314 of the ABCC6 protein (p.Arg1314Trp). This variant is present in population databases (rs63750759, gnomAD 0.3%). This missense change has been observed in individuals with pseudoxanthoma elasticum (PMID: 10835642, 16835894, 19339160, 30537162). ClinVar contains an entry for this variant (Variation ID: 6564). 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: 21935449, 23483032, 27994049). This variant disrupts the p.Arg1314 amino acid residue in ABCC6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29722917). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV001535919 | SCV001752567 | pathogenic | Autosomal recessive inherited pseudoxanthoma elasticum; Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of infancy, 2 | 2022-05-17 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000006942 | SCV000027138 | pathogenic | Autosomal recessive inherited pseudoxanthoma elasticum | 2012-01-13 | no assertion criteria provided | literature only | |
| OMIM | RCV000023273 | SCV000044564 | pathogenic | Arterial calcification, generalized, of infancy, 2 | 2012-01-13 | no assertion criteria provided | literature only | |
| PXE International | RCV000006942 | SCV000589091 | pathogenic | Autosomal recessive inherited pseudoxanthoma elasticum | 2021-03-01 | no assertion criteria provided | research |