ClinVar Miner

Submissions for variant NM_004646.4(NPHS1):c.609-2A>C

dbSNP: rs386833955
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000049930 SCV000800329 pathogenic Finnish congenital nephrotic syndrome 2018-05-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001034959 SCV001198262 likely pathogenic not provided 2019-02-18 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 5 of the NPHS1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with congential nephrotic syndrome (PMID: 18614772, 25720465). ClinVar contains an entry for this variant (Variation ID: 56517). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NPHS1 are known to be pathogenic (PMID: 11317351, 11854170, 12039988). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049930 SCV000082339 probable-pathogenic Finnish congenital nephrotic syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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