Submissions for variant NM_004646.4(NPHS1):c.1103C>T (p.Pro368Leu)

gnomAD frequency: 0.00001  dbSNP: rs386833867

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV000049837	SCV002020151	likely pathogenic	Finnish congenital nephrotic syndrome	2020-04-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001853052	SCV002278519	likely pathogenic	not provided	2023-11-06	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 368 of the NPHS1 protein (p.Pro368Leu). This variant is present in population databases (rs386833867, gnomAD 0.01%). This missense change has been observed in individual(s) with NPHS1-related conditions (PMID: 22732337, 23595123, 29869118). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56424). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NPHS1 protein function with a positive predictive value of 95%. 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.
Baylor Genetics	RCV000049837	SCV004191409	likely pathogenic	Finnish congenital nephrotic syndrome	2024-02-03	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000049837	SCV004810383	likely pathogenic	Finnish congenital nephrotic syndrome	2024-04-04	criteria provided, single submitter	clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049837	SCV000082246	probable-pathogenic	Finnish congenital nephrotic syndrome		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.