MYH9 R1400W - GET-Evidence

Curation:
Currentness:

MYH9 R1400W

(MYH9 Arg1400Trp)


Short summary

Probably a rare nonpathogenic polymorphism.

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect

Functional

No literature.

Case/Control

No statistics found.

Familial 1

Seen in unaffected father.

See Arrondel C et al. 2002 (11752022).

 
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

unknown

Summary of published research, and additional commentary

Arrondel et al. 2002 report finding this variant in an Epstein syndrome case (dominant inheritance), but another variant (S96L) was also present. S96L was a de novo mutation thought to be pathogenic by the authors. R1400W was inherited from the father, who was unaffected, and so was unlikely to be disease-causing. Because the variant was not present in 140 control chromosomes, the authors did not rule out a potential pathogenic impact or modifying effect.

This variant is also present in a HapMap individual, NA12878. Based on this and the presence of the variant in an unaffected father, this variant appears to be a rare polymorphism with no severe pathogenic effect.

Allele frequency

  • A @ chr22:36688178: 0.1% (16/10758) in EVS
  • A @ chr22:35018123: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 0.1% (16/10758)

Publications
 

Arrondel C, Vodovar N, Knebelmann B, Grünfeld JP, Gubler MC, Antignac C, Heidet L. Expression of the nonmuscle myosin heavy chain IIA in the human kidney and screening for MYH9 mutations in Epstein and Fechtner syndromes. J Am Soc Nephrol. 2002 Jan;13(1):65-74. PubMed PMID: 11752022.

This variant was seen along with another variant (S96L) in a patient with Epstein syndrome (which has autosomal dominant inheritance). The S96L variant was a de novo mutation and thought to be disease-causing by the authors, while this variant (R1400W) was inherited from the father (who was unaffected).

The authors provide arguments against R1400W having a pathogenic effect (the position is less conserved that S96, and the father was unaffected), but they weren’t comfortable entirely ruling out a pathogenic role because they did not see it once in 140 control chromosomes.

Genomes
 

Other external references
 

    GeneTests
  • GeneTests records for the MYH9 gene
    Nonsyndromic Hearing Loss and Deafness, Autosomal Dominant
    DFNA17 Nonsyndromic Hearing Loss and Deafness
    Epstein Syndrome
    Fechtner Syndrome
    May-Hegglin Anomaly
    MYH9-Related Disorders
    Sebastian Syndrome
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MYH9
    PolyPhen-2
  • Score: 0.986 (probably damaging)
    Web search results (5 hits -- see all)
  • Expression of the Nonmuscle Myosin Heavy Chain IIA in the ...
    Mutations in the MYH9 gene, which encodes the nonmuscle myosin heavy chain IIA, ... Indeed, mutations in the MYH9 gene, which encodes the nonmuscle myosin heavy ...
    jasn.asnjournals.org/cgi/content/full/13/1/65
  • Type III 98%
    ... kinase family Removed kinase gruop Effect Reference(s) for variant Reference(s) for ... Polymorphism (dbSNP:rs4974539) 2378615 MYH9 P35579 R1400W 1398 VAR_018315 CAMKL (0.622) ...
    nih.go.kr/phosphovariant/html/family_whole/TypeIII_98.txt
  • Type III 97%
    ... family Removed kinase gruop Effect Reference(s) for variant Reference(s) for phosphorylation site TPSD1 ... (dbSNP:rs36686) 11042166 MYH9 P35579 R1400W 1398 VAR_018315 CAMKL (0. ...
    nih.go.kr/phosphovariant/html/family_whole/TypeIII_97.txt

Other in silico analyses
 

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in