Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000503566 | SCV000597981 | likely pathogenic | Wolfram syndrome | 2016-05-11 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001857186 | SCV002236670 | pathogenic | not provided | 2022-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 885 of the WFS1 protein (p.Pro885Leu). This variant is present in population databases (rs372855769, gnomAD 0.004%). This missense change has been observed in individuals with autosomal recessive Wolfram syndrome (PMID: 10521293, 28432734). ClinVar contains an entry for this variant (Variation ID: 437297). 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 WFS1 protein function. Experimental studies have shown that this missense change affects WFS1 function (PMID: 16806192). For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV002506232 | SCV002807350 | likely pathogenic | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2021-11-18 | criteria provided, single submitter | clinical testing | |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV003233655 | SCV003932158 | pathogenic | Wolfram syndrome 1 | 2023-02-28 | criteria provided, single submitter | clinical testing | PS3, PM1, PM2, PM3_Supporting, PP3 |
Rady Children's Institute for Genomic Medicine, |
RCV003335435 | SCV004046440 | pathogenic | Autosomal dominant nonsyndromic hearing loss 6 | criteria provided, single submitter | clinical testing | This variant has been previously reported as a heterozygous and homozygous change in patients with Wolfram-like Syndrome/ Wolfram Syndrome (PMID: 10521293, 30773290, 28432734). In vitro analysis illustrated that the c.2654C>T (p.Pro885Leu) variant results in reduce protein expression affecting WFS1 function (PMID: 16806192). The c.2654C>T (p.Pro885Leu) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.001% (3/249382) and thus is presumed to be rare. The c.2654C>T (p.Pro885Leu) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.2654C>T (p.Pro885Leu) variant is classified as Pathogenic. | |
Ce |
RCV001857186 | SCV004185219 | likely pathogenic | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | WFS1: PM2, PM3, PP4, PS3:Supporting |
Yale Center for Mendelian Genomics, |
RCV001849390 | SCV002106595 | likely pathogenic | Wolfram-like syndrome | 2019-02-14 | no assertion criteria provided | literature only |