MED25 A335V - GET-Evidence

Curation:
Currentness:

MED25 A335V

(MED25 Ala335Val)


Short summary

Proposed by Leal et al 2009 to cause recessive Charcot-Marie-Tooth disorder in an extended Costa Rican family. (Reported via OMIM to ClinVar, see: http://www.ncbi.nlm.nih.gov/clinvar/RCV000001387/) According to ExAC allele frequency data, we would expect 1 in 25,000 to 30,000 people to be homozygous for this variant. Charcot-Marie-Tooth type 2 has a prevalence of 1 in 10,000. If this hypothesis were true, homozygosity this variant alone would theoretically account for more than a third of cases. As such we would expect strong evidence in literature for an effect, but we have only a single report of a family (where linkage can confound analysis) and no other reports.

Variant evidence
Computational -
Functional -
Case/Control 4

High allele frequency contradicts proposed pathogenic effect

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Allele frequency

  • None available.

Publications
 

Leal A, Huehne K, Bauer F, Sticht H, Berger P, Suter U, Morera B, Del Valle G, Lupski JR, Ekici A, Pasutto F, Endele S, Barrantes R, Berghoff C, Berghoff M, Neundörfer B, Heuss D, Dorn T, Young P, Santolin L, Uhlmann T, Meisterernst M, Sereda MW, Stassart RM, Zu Horste GM, Nave KA, Reis A, Rautenstrauss B. Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models. Neurogenetics. 2009 Oct;10(4):375-376. PubMed PMID: 25488817; PubMed Central PMCID: PMC2847162.

 

Genomes
 

Other in silico analyses
 

  • NBLOSUM100 score = 2
  • GET-Evidence autoscore = 1

Edit history
 

Gene search

"GENE" or "GENE A123C":

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