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NM_203475.3(PORCN):c.370C>T (p.Arg124Ter) AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 16, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000599522.3

Allele description [Variation Report for NM_203475.3(PORCN):c.370C>T (p.Arg124Ter)]

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

Gene:
PORCN:porcupine O-acyltransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp11.23
Genomic location:
Preferred name:
NM_203475.3(PORCN):c.370C>T (p.Arg124Ter)
HGVS:
  • NC_000023.11:g.48511932C>T
  • NG_009278.1:g.7950C>T
  • NM_001282167.2:c.157C>T
  • NM_022825.4:c.370C>T
  • NM_203473.3:c.370C>T
  • NM_203474.1:c.370C>T
  • NM_203475.3:c.370C>TMANE SELECT
  • NP_001269096.1:p.Arg53Ter
  • NP_073736.2:p.Arg124Ter
  • NP_982299.1:p.Arg124Ter
  • NP_982300.1:p.Arg124Ter
  • NP_982301.1:p.Arg124Ter
  • NC_000023.10:g.48370320C>T
  • NM_203475.1:c.370C>T
Protein change:
R124*; ARG124TER
Links:
OMIM: 300651.0003; dbSNP: rs137852218
NCBI 1000 Genomes Browser:
rs137852218
Molecular consequence:
  • NM_001282167.2:c.157C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_022825.4:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_203473.3:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_203474.1:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_203475.3:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000709912GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Feb 14, 2018) 		germlineclinical testing

Citation Link,

SCV004300007Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 16, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia.

Wang X, Reid Sutton V, Omar Peraza-Llanes J, Yu Z, Rosetta R, Kou YC, Eble TN, Patel A, Thaller C, Fang P, Van den Veyver IB.

Nat Genet. 2007 Jul;39(7):836-8. Epub 2007 Jun 3.

PubMed [citation]
PMID:
17546030

PORCN mutations in focal dermal hypoplasia: coping with lethality.

Bornholdt D, Oeffner F, König A, Happle R, Alanay Y, Ascherman J, Benke PJ, Boente Mdel C, van der Burgt I, Chassaing N, Ellis I, Francisco CR, Della Giovanna P, Hamel B, Has C, Heinelt K, Janecke A, Kastrup W, Loeys B, Lohrisch I, Marcelis C, Mehraein Y, et al.

Hum Mutat. 2009 May;30(5):E618-28. doi: 10.1002/humu.20992. Erratum in: Hum Mutat. 2009 Oct;30(10):1472-3.

PubMed [citation]
PMID:
19309688
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000709912.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004300007.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024