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NM_181882.3(PRX):c.2145T>A (p.Cys715Ter) AND Charcot-Marie-Tooth disease type 4

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 21, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000474032.10

Allele description [Variation Report for NM_181882.3(PRX):c.2145T>A (p.Cys715Ter)]

NM_181882.3(PRX):c.2145T>A (p.Cys715Ter)

Gene:
PRX:periaxin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_181882.3(PRX):c.2145T>A (p.Cys715Ter)
HGVS:
  • NC_000019.10:g.40396207A>T
  • NG_007979.1:g.22158T>A
  • NM_020956.2:c.*2350T>A
  • NM_181882.3:c.2145T>AMANE SELECT
  • NP_870998.2:p.Cys715Ter
  • NP_870998.2:p.Cys715Ter
  • LRG_265t1:c.*2350T>A
  • LRG_265t2:c.2145T>A
  • LRG_265:g.22158T>A
  • LRG_265p2:p.Cys715Ter
  • NC_000019.9:g.40902114A>T
  • NM_181882.2:c.2145T>A
  • NM_181882.3:c.2145T>A
Protein change:
C715*; CYS715TER
Links:
OMIM: 605725.0006; dbSNP: rs104894707
NCBI 1000 Genomes Browser:
rs104894707
Molecular consequence:
  • NM_020956.2:c.*2350T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_181882.3:c.2145T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Charcot-Marie-Tooth disease type 4
Synonyms:
Charcot-Marie-Tooth, Type 4
Identifiers:
MONDO: MONDO:0018995; MedGen: C4082197

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000551379Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 21, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Periaxin mutation causes early-onset but slow-progressive Charcot-Marie-Tooth disease.

Kijima K, Numakura C, Shirahata E, Sawaishi Y, Shimohata M, Igarashi S, Tanaka T, Hayasaka K.

J Hum Genet. 2004;49(7):376-379. doi: 10.1007/s10038-004-0162-3. Epub 2004 Jun 12.

PubMed [citation]
PMID:
15197604

Clinicopathological and genetic study of early-onset demyelinating neuropathy.

Parman Y, Battaloglu E, Baris I, Bilir B, Poyraz M, Bissar-Tadmouri N, Williams A, Ammar N, Nelis E, Timmerman V, De Jonghe P, Najafov A, Deymeer F, Serdaroglu P, Brophy PJ, Said G.

Brain. 2004 Nov;127(Pt 11):2540-50. Epub 2004 Oct 6. Erratum in: Brain. 2007 Jul;130(7):1972. Necefov, Ayaz [corrected to Najafov, Ayaz].

PubMed [citation]
PMID:
15469949
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000551379.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PRX protein in which other variant(s) (p.Arg1070*) have been determined to be pathogenic (PMID: 15197604, 15469949, 16770524, 22847150, 26059842). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 4792). This premature translational stop signal has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 12112076). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs104894707, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Cys715*) in the PRX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 747 amino acid(s) of the PRX protein.

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

Last Updated: Apr 15, 2024