ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.3442C>T (p.Gln1148Ter) (rs150855173)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169477 SCV000220923 likely pathogenic Finnish congenital nephrotic syndrome 2014-11-26 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America RCV000169477 SCV000919901 pathogenic Finnish congenital nephrotic syndrome 2018-12-14 criteria provided, single submitter clinical testing Variant summary: NPHS1 c.3442C>T (p.Gln1148X) 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. A truncation downstream of this position have been classified as pathogenic by our laboratory (c.3478C>T (p.Arg1160X)). The variant allele was found at a frequency of 8.1e-06 in 246066 control chromosomes (gnomAD). c.3442C>T has been reported in the literature in multiple compound heterozygous individuals affected with congenital Nephrotic Syndrome, Type 1 (Beltcheva 2001, Schoeb 2010, Wong 2013, Bierzynska 2017). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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.
Invitae RCV001220457 SCV001392446 pathogenic not provided 2019-04-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1148*) in the NPHS1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs150855173, ExAC 0.003%). This variant has been observed in individuals affected with nephrotic syndrome (PMID: 23949594, 24902943). ClinVar contains an entry for this variant (Variation ID: 189074). Loss-of-function variants in NPHS1 are known to be pathogenic (PMID: 11317351, 11854170, 12039988). For these reasons, this variant has been classified as Pathogenic.

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