Variant position:  219

Type of variant:  LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

Residue change:  From Tyrosine (Y) to Histidine (H) at position 219 (Y219H, p.Tyr219His).

Physico-chemical properties:  Change from large size and aromatic (Y) to medium size and polar (H)

BLOSUM score:  2

Variant description:  In AGS2; heterozygous compound with a nonsense mutation; reduces stability of the RNase complex.

Other resources:  

• Variant rs77391331 [ dbSNP | Ensembl ]

Variant position:  219

Protein sequence length:  312

Location on the sequence:   QASTDKEEDYIRYAHGLISD  Y IPKELSDDLSKYLKLPEPSA

Residue conservation: 

Human                         QASTDKEEDYIRYAHGLISDYIPKELSDDLSKYL-KLPEPSA

Mouse                         QVSRDKEEDYVRYAHGLISDYIPKELSDDLSKFL-KLPEPP

Rat                           QVSRDKEEDYVRYAHGLISDYIPKELSDDLSKLL-KLPEPP

Bovine                        QVSSDKDEDYVRYAHGLISDYIPKQLSDDLSKYL-KLPEPP

Xenopus laevis                QGSDVKEEDYTRYAHGLISEYLTEDLREDLSKYL-GLPDLS

Xenopus tropicalis            QGSDVKEEDYTRYAHGLISEYLTEDLREDLSKYL-GLPDLS

Baker's yeast                 APTEIKQCYKVVMATNLLVSLIPRAAYHNLLTFS---PTMD

Fission yeast                 LPQDLLELSCKWHAASLVCEDLQPEWYNKLAYWQEELAPLH

Sequence annotation in neighborhood:  

The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutieres syndrome defects.
Figiel M.; Chon H.; Cerritelli S.M.; Cybulska M.; Crouch R.J.; Nowotny M.;
J. Biol. Chem. 286:10540-10550(2011)
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 14-233; SUBUNIT; FUNCTION; CHARACTERIZATION OF VARIANTS AGS2 LEU-73; SER-83; ARG-86 AND HIS-219;

Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection.
Crow Y.J.; Leitch A.; Hayward B.E.; Garner A.; Parmar R.; Griffith E.; Ali M.; Semple C.; Aicardi J.; Babul-Hirji R.; Baumann C.; Baxter P.; Bertini E.; Chandler K.E.; Chitayat D.; Cau D.; Dery C.; Fazzi E.; Goizet C.; King M.D.; Klepper J.; Lacombe D.; Lanzi G.; Lyall H.; Martinez-Frias M.L.; Mathieu M.; McKeown C.; Monier A.; Oade Y.; Quarrell O.W.; Rittey C.D.; Rogers R.C.; Sanchis A.; Stephenson J.B.P.; Tacke U.; Till M.; Tolmie J.L.; Tomlin P.; Voit T.; Weschke B.; Woods C.G.; Lebon P.; Bonthron D.T.; Ponting C.P.; Jackson A.P.;
Nat. Genet. 38:910-916(2006)
Cited for: VARIANTS AGS2 ARG-60; ARG-86; THR-162; ILE-163; THR-177; GLY-185 AND HIS-219; FUNCTION; TISSUE SPECIFICITY; INTERACTION WITH RNASEH2A AND RNASEH2C;

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.
Rice G.; Patrick T.; Parmar R.; Taylor C.F.; Aeby A.; Aicardi J.; Artuch R.; Montalto S.A.; Bacino C.A.; Barroso B.; Baxter P.; Benko W.S.; Bergmann C.; Bertini E.; Biancheri R.; Blair E.M.; Blau N.; Bonthron D.T.; Briggs T.; Brueton L.A.; Brunner H.G.; Burke C.J.; Carr I.M.; Carvalho D.R.; Chandler K.E.; Christen H.J.; Corry P.C.; Cowan F.M.; Cox H.; D'Arrigo S.; Dean J.; De Laet C.; De Praeter C.; Dery C.; Ferrie C.D.; Flintoff K.; Frints S.G.; Garcia-Cazorla A.; Gener B.; Goizet C.; Goutieres F.; Green A.J.; Guet A.; Hamel B.C.; Hayward B.E.; Heiberg A.; Hennekam R.C.; Husson M.; Jackson A.P.; Jayatunga R.; Jiang Y.H.; Kant S.G.; Kao A.; King M.D.; Kingston H.M.; Klepper J.; van der Knaap M.S.; Kornberg A.J.; Kotzot D.; Kratzer W.; Lacombe D.; Lagae L.; Landrieu P.G.; Lanzi G.; Leitch A.; Lim M.J.; Livingston J.H.; Lourenco C.M.; Lyall E.G.; Lynch S.A.; Lyons M.J.; Marom D.; McClure J.P.; McWilliam R.; Melancon S.B.; Mewasingh L.D.; Moutard M.L.; Nischal K.K.; Ostergaard J.R.; Prendiville J.; Rasmussen M.; Rogers R.C.; Roland D.; Rosser E.M.; Rostasy K.; Roubertie A.; Sanchis A.; Schiffmann R.; Scholl-Burgi S.; Seal S.; Shalev S.A.; Corcoles C.S.; Sinha G.P.; Soler D.; Spiegel R.; Stephenson J.B.; Tacke U.; Tan T.Y.; Till M.; Tolmie J.L.; Tomlin P.; Vagnarelli F.; Valente E.M.; Van Coster R.N.; Van der Aa N.; Vanderver A.; Vles J.S.; Voit T.; Wassmer E.; Weschke B.; Whiteford M.L.; Willemsen M.A.; Zankl A.; Zuberi S.M.; Orcesi S.; Fazzi E.; Lebon P.; Crow Y.J.;
Am. J. Hum. Genet. 81:713-725(2007)
Cited for: VARIANTS AGS2 HIS-43; ARG-60; LEU-73; SER-83; ARG-86; PHE-138; ILE-159; THR-162; ILE-163; THE-177; MET-183; GLY-185 AND HIS-219;