ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.2479C>T (p.Arg827Ter) (rs140018064)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000780551 SCV000917911 pathogenic Finnish congenital nephrotic syndrome 2018-08-09 criteria provided, single submitter clinical testing Variant summary: NPHS1 c.2479C>T (p.Arg827X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.3250dupG (p.Val1084fsX12), c.3325C>T (p.Arg1109X), c.3478C>T (p.Arg1160X)). The variant allele was found at a frequency of 2e-05 in 246522 control chromosomes (gnomAD). c.2479C>T has been reported in the literature in individuals affected with Nephrotic Syndrome, Type 1 (Schultheiss 2004, Philippe 2008, Machuca 2010, Aya 2009). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, demonstrating a truncated protein product and defective trafficking to the cell surface (Miyai 2014). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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