ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.319G>A (p.Ala107Thr) (rs386833933)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000049907 SCV000914839 uncertain significance Finnish congenital nephrotic syndrome 2018-11-03 criteria provided, single submitter clinical testing The NPHS1 c.319G>A (p.Ala107Thr) variant has been reported in a compound heterozygous state with a splice site variant in one individual with congenital Finnish nephrosis (Philippe et al. 2008). The p.Ala107Thr variant was absent from 188 control chromosomes, but is reported at a frequency of 0.000027 in the European (non-Finnish) population from the Genome Aggregation Database. Functional studies in HeLa cells demonstrated that the p.Ala107Thr variant protein localized to the plasma membrane with wild type nephrin. In HEK293 cells, co-immunoprecipitation studies showed that both nephrin homodimerization and NEPH1 heterodimerization were intact and unaffected by the p.Ala107Thr variant (Philippe et al. 2008). Based on the limited evidence, the p.Ala107Thr variant is classified as a variant of unknown significance but suspicious for pathogenicity for congenital nephrotic syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049907 SCV000082316 probable-pathogenic Finnish congenital nephrotic syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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