NM_000532.5(PCCB):c.517_518del (p.Leu173fs) AND Propionic acidemia

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 16, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000667712.4

Allele description [Variation Report for NM_000532.5(PCCB):c.517_518del (p.Leu173fs)]

NM_000532.5(PCCB):c.517_518del (p.Leu173fs)

Gene:
PCCB:propionyl-CoA carboxylase subunit beta [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
3q22.3
Genomic location:
Preferred name:
NM_000532.5(PCCB):c.517_518del (p.Leu173fs)
HGVS:
  • NC_000003.11:g.135980880_135980881del
  • NC_000003.12:g.136262039_136262040del
  • NG_008939.1:g.16715_16716del
  • NM_000532.5:c.517_518delMANE SELECT
  • NM_001178014.1:c.577_578del
  • NP_000523.2:p.Leu173fs
  • NP_001171485.1:p.Leu193fs
  • NC_000003.11:g.135980880_135980881del
  • NC_000003.11:g.135980880_135980881delTT
  • NC_000003.11:g.135980881_135980882del
  • NM_000532.4:c.517_518del
  • NM_000532.4:c.517_518delTT
Protein change:
L173fs
Links:
dbSNP: rs755776820
NCBI 1000 Genomes Browser:
rs755776820
Molecular consequence:
  • NM_000532.5:c.517_518del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001178014.1:c.577_578del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Propionic acidemia (PROP)
Synonyms:
Propionyl-CoA carboxylase deficiency; PCC deficiency; Glycinemia, ketotic; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011628; MedGen: C0268579; Orphanet: 35; OMIM: 606054; Human Phenotype Ontology: HP:0003353

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000792206Counsylcriteria provided, single submitter
Likely pathogenic
(Jun 9, 2017)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV001136607Mendelicscriteria provided, single submitter
Pathogenic
(May 28, 2019)
unknownclinical testing

Citation Link,

SCV001399808Invitaecriteria provided, single submitter
Pathogenic
(Oct 16, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Short-term outcome of propionic aciduria treated at presentation with N-carbamylglutamate: a retrospective review of four patients.

Lévesque S, Lambert M, Karalis A, Melancon S, Russell L, Braverman N.

JIMD Rep. 2012;2:97-102. doi: 10.1007/8904_2011_54. Epub 2011 Sep 6.

PubMed [citation]
PMID:
23430860
PMCID:
PMC3509846

Propionic acidemia: mutation update and functional and structural effects of the variant alleles.

Desviat LR, Pérez B, Pérez-Cerdá C, Rodríguez-Pombo P, Clavero S, Ugarte M.

Mol Genet Metab. 2004 Sep-Oct;83(1-2):28-37. Review.

PubMed [citation]
PMID:
15464417
See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000792206.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Mendelics, SCV001136607.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001399808.2

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

Description

This sequence change creates a premature translational stop signal (p.Leu173Glyfs*56) in the PCCB gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with propionic acidemia (PMID: 23430860). ClinVar contains an entry for this variant (Variation ID: 552452). Loss-of-function variants in PCCB are known to be pathogenic (PMID: 15464417). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 7, 2021

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