NM_004646.4(NPHS1):c.1379G>A (p.Arg460Gln) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 3, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001388275.30

Allele description [Variation Report for NM_004646.4(NPHS1):c.1379G>A (p.Arg460Gln)]

NM_004646.4(NPHS1):c.1379G>A (p.Arg460Gln)

Gene:

NPHS1:NPHS1 adhesion molecule, nephrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.12

Genomic location:

Preferred name:

NM_004646.4(NPHS1):c.1379G>A (p.Arg460Gln)

HGVS:

NC_000019.10:g.35848102C>T
NG_013356.2:g.26186G>A
NG_051206.1:g.1468C>T
NM_004646.4:c.1379G>AMANE SELECT
NP_004637.1:p.Arg460Gln
NP_004637.1:p.Arg460Gln
LRG_693t1:c.1379G>A
LRG_693:g.26186G>A
LRG_693p1:p.Arg460Gln
NC_000019.9:g.36339004C>T
NM_004646.3:c.1379G>A
O60500:p.Arg460Gln

Protein change:

R460Q

Links:

UniProtKB: O60500#VAR_064209; dbSNP: rs386833880

Molecular consequence:

NM_004646.4:c.1379G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001589205	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2025)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19194555, 21125408, 21415313, 30655312, 28492532
SCV004145519	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Nov 1, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001589205

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2025)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004145519

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Nov 1, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Two Korean infants with genetically confirmed congenital nephrotic syndrome of Finnish type.

Lee BH, Ahn YH, Choi HJ, Kang HK, Kim SD, Cho BS, Moon KC, Ha IS, Cheong HI, Choi Y.

J Korean Med Sci. 2009 Jan;24 Suppl(Suppl 1):S210-4. doi: 10.3346/jkms.2009.24.S1.S210. Epub 2009 Jan 28.

PubMed [citation]

PMID:: 19194555
PMCID:: PMC2633182

Novel mutations in steroid-resistant nephrotic syndrome diagnosed in Tunisian children.

Mbarek IB, Abroug S, Omezzine A, Pawtowski A, Gubler MC, Bouslama A, Harbi A, Antignac C.

Pediatr Nephrol. 2011 Feb;26(2):241-9. doi: 10.1007/s00467-010-1694-8. Epub 2010 Dec 2.

PubMed [citation]

PMID:: 21125408

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001589205.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 460 of the NPHS1 protein (p.Arg460Gln). This variant is present in population databases (rs386833880, gnomAD 0.003%). This missense change has been observed in individual(s) with nephrotic syndrome (PMID: 19194555, 21125408, 21415313, 30655312). 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: 56438). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV004145519.22

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

NPHS1: PM3:Very Strong, PM2, PS4:Moderate, PS3:Supporting, BP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jun 20, 2026

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