ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.791C>G (p.Pro264Arg) (rs34982899)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000179892 SCV000232209 benign not specified 2015-03-30 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000712435 SCV000842928 benign not provided 2018-02-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000179892 SCV000917909 benign not specified 2018-04-20 criteria provided, single submitter clinical testing Variant summary: NPHS1 c.791C>G (p.Pro264Arg) results in a non-conservative amino acid change located in the Immunoglobulin-like domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.015 in 275302 control chromosomes in the gnomAD database, including 54 homozygotes. The observed variant frequency is approximately 4.5 fold above the estimated maximal expected allele frequency for a pathogenic variant in NPHS1 causing Nephrotic Syndrome, Type 1 phenotype (0.0034), strongly suggesting that the variant is benign. c.791C>G has been reported in the literature in individuals affected with Nephrotic Syndrome, Type 1, without strong evidence for causality. In addition, the variant was found in a patient in cis with a likely pathogenic NPHS1 mutation, which was inherited from a healthy father, further supporting a benign role (Fylaktou_2013). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001125720 SCV001284822 likely benign Congenital nephrotic syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

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