Submissions for variant NM_004646.3(NPHS1):c.2404C>T (p.Arg802Trp) (rs386833911)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000793793	SCV000933166	likely pathogenic	not provided	2018-09-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with tryptophan at codon 802 of the NPHS1 protein (p.Arg802Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs386833911, ExAC 0.01%). This variant has been observed in several individuals affected with nephrotic syndrome (PMID: 9915943, 23595123, 25720465, 11854170). ClinVar contains an entry for this variant (Variation ID: 56471). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg802 amino acid residue in NPHS1. Other variant that disrupts this residue have been observed in affected individuals (PMID: 9915943), which suggests that this may be a clinically significant amino acid residue. 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)	RCV000049884	SCV000082293	probable-pathogenic	Finnish congenital nephrotic syndrome		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.