ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.619del (p.Arg207fs) (rs778217926)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000412108 SCV000485436 likely pathogenic Finnish congenital nephrotic syndrome 2015-12-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000412108 SCV000917906 likely pathogenic Finnish congenital nephrotic syndrome 2018-02-12 criteria provided, single submitter clinical testing Variant summary: NPHS1 c.619delC (p.Arg207GlyfsX28) 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 (eg. c.802C>T, p.Arg268X; c.3325C>T, p.Arg1109X; c.3478C>T, p.Arg1160X). The variant allele was found at a frequency of 8.1e-06 in 246004 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in NPHS1 causing Nephrotic Syndrome, Type 1 (8.1e-06 vs 3.40E-03), allowing no conclusion about variant significance. c.619delC has been reported in the literature in individuals affected with Nephrotic Syndrome, Type 1 (Machuca_2010, Wong_2013). These data indicate that the variant may be associated with disease. 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 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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