ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.1868G>T (p.Cys623Phe) (rs386833895)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000049866 SCV000220231 likely pathogenic Finnish congenital nephrotic syndrome 2014-04-08 criteria provided, single submitter literature only
Fulgent Genetics RCV000049866 SCV000893523 likely pathogenic Finnish congenital nephrotic syndrome 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000049866 SCV000411567 pathogenic Finnish congenital nephrotic syndrome 2017-04-27 criteria provided, single submitter clinical testing The NPHS1 c.1868G>T (p.Cys623Phe) variant has been reported in six studies and is found in a total of eight patients with congenital Finnish nephrosis, including in one patient in a homozygous state, six patients (including a sibling pair) in a compound heterozygous state, and one patient in a heterozygous state in whom a second variant was not detected (Lenkkeri et al. 1999; Koziell et al. 2002; Schultheiss et al. 2004; Santin et al. 2009; Buscher et al. 2010; Schoeb et al. 2010). The p.Cys623Phe variant was absent from 173 controls but is reported at a frequency of 0.00005 in the European (non-Finnish) population of the Exome Aggregation Consortium. Functional studies demonstrated impaired intracellular trafficking of the p.Cys623Phe variant protein with retention in the endoplasmic reticulum compared to localization of the wild type protein at the plasma membrane (Liu et al. 2001). Based on the collective evidence, the p.Cys623Phe variant is classified as pathogenic for congenital nephrotic syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049866 SCV000082275 probable-pathogenic Finnish congenital nephrotic syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.