NM_000532.5(PCCB):c.838dup (p.Leu280fs) AND Propionic acidemia

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 14, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000667695.3

Allele description [Variation Report for NM_000532.5(PCCB):c.838dup (p.Leu280fs)]

NM_000532.5(PCCB):c.838dup (p.Leu280fs)

Gene:
PCCB:propionyl-CoA carboxylase subunit beta [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
3q22.3
Genomic location:
Preferred name:
NM_000532.5(PCCB):c.838dup (p.Leu280fs)
HGVS:
  • NC_000003.12:g.136298026dup
  • NG_008939.1:g.52702dup
  • NM_000532.5:c.838dupMANE SELECT
  • NM_001178014.2:c.898dup
  • NP_000523.2:p.Leu280fs
  • NP_001171485.1:p.Leu300fs
  • NC_000003.11:g.136016864_136016865insC
  • NC_000003.11:g.136016868dup
  • NM_000532.4:c.838dup
  • NM_000532.4:c.838dupC
Protein change:
L280fs
Links:
dbSNP: rs769968548
NCBI 1000 Genomes Browser:
rs769968548
Molecular consequence:
  • NM_000532.5:c.838dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001178014.2:c.898dup - 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
SCV000792186Counsylcriteria provided, single submitter
Likely pathogenic
(Jun 9, 2017)
unknownclinical testing

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

Citation Link,

SCV001214519Invitaecriteria provided, single submitter
Pathogenic
(Aug 14, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Two frequent mutations associated with the classic form of propionic acidemia in Taiwan.

Chiu YH, Liu YN, Liao WL, Chang YC, Lin SP, Hsu CC, Chiu PC, Niu DM, Wang CH, Ke YY, Chien YH, Hsiao KJ, Liu TT.

Biochem Genet. 2014 Oct;52(9-10):415-29. doi: 10.1007/s10528-014-9657-6. Epub 2014 May 27.

PubMed [citation]
PMID:
24863100

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, SCV000792186.1

#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 Invitae, SCV001214519.2

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

Description

This sequence change creates a premature translational stop signal (p.Leu280Profs*11) in the PCCB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs769968548, ExAC 0.01%). This variant has been observed in an individual with propionic acidemia (PMID: 24863100). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 552435). 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 24, 2021

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