Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
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 |