ClinVar Miner

Submissions for variant NM_203475.3(PORCN):c.370C>T (p.Arg124Ter)

dbSNP: rs137852218
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599522 SCV000709912 pathogenic not provided 2018-02-14 criteria provided, single submitter clinical testing The R124X nonsense variant in the PORCN gene has been reported previously in association with Goltz syndrome including as a de novo occurrence (Grzeschik et al., 2007; Bornholdt et al., 2009; Lombardi et al., 2011; Wang et al., 2007). The variant is not observed in large population cohorts (Lek et al., 2016). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Functional studies of the R124X variant have shown that it impairs normal WNT3A secretions and may subsequently impact Wnt signaling (Liu et al., 2012).
Fulgent Genetics, Fulgent Genetics RCV000011448 SCV002810959 pathogenic Focal dermal hypoplasia 2022-03-16 criteria provided, single submitter clinical testing
Invitae RCV000599522 SCV004300007 pathogenic not provided 2022-11-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 10702). This premature translational stop signal has been observed in individual(s) with focal dermal hypoplasia (PMID: 17546030). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg124*) in the PORCN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PORCN are known to be pathogenic (PMID: 17546030, 19309688).
OMIM RCV000011448 SCV000031680 pathogenic Focal dermal hypoplasia 2007-07-01 no assertion criteria provided literature only

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