ClinVar Miner

Submissions for variant NM_004646.4(NPHS1):c.1715G>A (p.Ser572Asn)

gnomAD frequency: 0.00001  dbSNP: rs386833889
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487117 SCV000568764 pathogenic not provided 2020-02-24 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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: 15906409, 20172850, 27019444, 20507940)
Counsyl RCV000049860 SCV000789515 likely pathogenic Finnish congenital nephrotic syndrome 2017-02-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000487117 SCV001233250 pathogenic not provided 2023-02-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser572 amino acid residue in NPHS1. Other variant(s) that disrupt this residue have been observed in individuals with NPHS1-related conditions (PMID: 18503012, 26248470), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 56447). This missense change has been observed in individual(s) with congenital nephrotic syndrome (PMID: 15906409, 20172850, 29474669). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs386833889, gnomAD 0.002%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 572 of the NPHS1 protein (p.Ser572Asn).
Fulgent Genetics, Fulgent Genetics RCV000049860 SCV002813939 likely pathogenic Finnish congenital nephrotic syndrome 2022-03-11 criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049860 SCV000082269 probable-pathogenic Finnish congenital nephrotic syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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