Submissions for variant NM_004646.4(NPHS1):c.515_517del (p.Thr172del)

dbSNP: rs386833947

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000049922	SCV000221070	likely pathogenic	Finnish congenital nephrotic syndrome	2015-01-22	criteria provided, single submitter	literature only
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000049922	SCV000680319	likely pathogenic	Finnish congenital nephrotic syndrome	2017-12-07	criteria provided, single submitter	clinical testing
Mendelics	RCV000049922	SCV001141052	pathogenic	Finnish congenital nephrotic syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000049922	SCV001362147	pathogenic	Finnish congenital nephrotic syndrome	2019-09-19	criteria provided, single submitter	clinical testing	Variant summary: NPHS1 c.515_517delCCA (p.Thr172del) results in an in-frame deletion that is predicted to remove a threonine residue from the second immunoglobulin-like domain (IPR013162) of the encoded protein. The variant allele was found at a frequency of 8e-06 in 251116 control chromosomes (gnomAD). c.515_517delCCA has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Nephrotic Syndrome, Type 1 (e.g. Buscher_2010, Machuca_2010). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268096	SCV001446749	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001268096	SCV001592882	pathogenic	not provided	2023-12-20	criteria provided, single submitter	clinical testing	This variant, c.515_517del, results in the deletion of 1 amino acid(s) of the NPHS1 protein (p.Thr172del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs386833947, gnomAD 0.006%). This variant has been observed in individual(s) with congential nephrotic syndrome (PMID: 9915943, 20507940, 20798252, 26560236). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.515delCCA. ClinVar contains an entry for this variant (Variation ID: 56509). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000049922	SCV003816065	uncertain significance	Finnish congenital nephrotic syndrome	2020-03-16	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000049922	SCV004191408	pathogenic	Finnish congenital nephrotic syndrome	2023-12-29	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000049922	SCV004806555	likely pathogenic	Finnish congenital nephrotic syndrome	2024-03-26	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000049922	SCV005051893	pathogenic	Finnish congenital nephrotic syndrome	2024-02-01	criteria provided, single submitter	curation
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049922	SCV000082331	probable-pathogenic	Finnish congenital nephrotic syndrome		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.
Natera, Inc.	RCV000049922	SCV002087109	pathogenic	Finnish congenital nephrotic syndrome	2020-07-10	no assertion criteria provided	clinical testing
Yale Center for Mendelian Genomics, Yale University	RCV001849306	SCV002106813	likely pathogenic	Nephrotic syndrome	2017-11-10	no assertion criteria provided	literature only