ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.1307_1308dup (p.Val437fs) (rs386833878)

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 RCV000049849 SCV000486280 likely pathogenic Finnish congenital nephrotic syndrome 2016-05-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000049849 SCV000917905 likely pathogenic Finnish congenital nephrotic syndrome 2018-02-12 criteria provided, single submitter clinical testing Variant summary: NPHS1 c.1307_1308dupAC (p.Val437ThrfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2541delT (p.Lys848fsX57), c.3325C>T (p.Arg1109X), c.3478C>T (p.Arg1160X)). The variant allele was found at a frequency of 4.1e-06 in 246230 control chromosomes, which does not exceed the maximal expected allele frequency for a pathogenic mutation in NPHS1. The c.1307_1308dupAC variant has been reported in the literature in individuals affected with Nephrotic Syndrome, Type 1 (Sadowski 2015), including one homozygous patient (Kestila 1998). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV000049849 SCV000027467 pathogenic Finnish congenital nephrotic syndrome 1998-03-01 no assertion criteria provided literature only
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049849 SCV000082258 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.