ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.3325C>T (p.Arg1109Ter) (rs137853042)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000007270 SCV000698506 pathogenic Finnish congenital nephrotic syndrome 2016-10-31 criteria provided, single submitter clinical testing Variant summary: The NPHS1 c.3325C>T (p.Arg1109X) variant, also known as Fin-minor, results in a premature termination codon, predicted to cause a truncated or absent NPHS1 protein due to nonsense mediated decay (NMD), which are commonly known mechanisms for disease. This variant was found in 25/121560 control chromosomes at a frequency of 0.0002057, which is lower than the estimated maximal expected allele frequency of a pathogenic NPHS1 variant (0.0033541). This variant is a known pathogenic variant with consistent genotype-phenotype data and the variant is mainly found in Finnish population (Kestila_1998, Lenkkeri_1999, Patrakka_2000, Koziell_2002, Machuca_2010, Sadowski_2015). In vitro functional assay shows that this variant abrogates the binding of the protein to podocin (Huber_2003). Taken together, this variant is classified as Pathogenic.
Myriad Women's Health, Inc. RCV000007270 SCV001194169 pathogenic Finnish congenital nephrotic syndrome 2019-12-11 criteria provided, single submitter clinical testing NM_004646.3(NPHS1):c.3325C>T(R1109*, aka Fin minor) is classified as pathogenic in the context of nephrotic syndrome, NPHS1-related. Sources cited for classification include the following: PMID 20507940, 11854170, 10972661, 20172850, 9915943 and 9660941. Classification of NM_004646.3(NPHS1):c.3325C>T(R1109*, aka Fin minor) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
OMIM RCV000007270 SCV000027466 pathogenic Finnish congenital nephrotic syndrome 2002-02-15 no assertion criteria provided literature only

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