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UniProtKB/Swiss-Prot P22033: Variant p.Asn219Tyr

Methylmalonyl-CoA mutase, mitochondrial
Gene: MMUT
Variant information

Variant position:  219
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Asparagine (N) to Tyrosine (Y) at position 219 (N219Y, p.Asn219Tyr).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (N) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In MMAM; mut0; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  219
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  750
The length of the canonical sequence.

Location on the sequence:   FIVTGEEQGVPKEKLTGTIQ  N DILKEFMVRNTYIFPPEPSM
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         FIVTGEEQGVPKEKLTGTIQNDILKEFMVRNTYIFPPEPSM

Mouse                         FIVTGEEQGVPKEKLTGTIQNDILKEFMVRNTYIFPPEPSM

Pig                           FIVSGEEQGVPKEKLTGTIQNDILKEFMVRNTYIFPPEPSM

Bovine                        FIVTGEEQGVPKEKLTGTIQNDILKEFMVRNTYIFPPEPSM

Caenorhabditis elegans        YVVAAEEAGVSRKLLAGTIQNDILKEFMVRNTYIYPPEPSM

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 33 – 750 Methylmalonyl-CoA mutase, mitochondrial
Binding site 228 – 228 malonyl-CoA
Modified residue 212 – 212 N6-acetyllysine


Literature citations

Mutation analysis of the MCM gene in Israeli patients with mut(0) disease.
Berger I.; Shaag A.; Anikster Y.; Baumgartner E.R.; Bar-Meir M.; Joseph A.; Elpeleg O.N.;
Mol. Genet. Metab. 73:107-110(2001)
Cited for: VARIANT MMAM TYR-219; VARIANTS THR-499 AND VAL-671;

Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.
Acquaviva C.; Benoist J.-F.; Pereira S.; Callebaut I.; Koskas T.; Porquet D.; Elion J.;
Hum. Mutat. 25:167-176(2005)
Cited for: VARIANTS MMAM HIS-108; LEU-148; ASN-156; VAL-158; GLU-191; ARG-203; SER-215; TYR-219; ASN-262; PRO-293; PHE-328; CYS-587; THR-615; ASN-621; ARG-623; ARG-624; ARG-627; GLU-637; ILE-638; TYR-640; ARG-642; TRP-694 AND LYS-700;

Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants.
Martinez M.A.; Rincon A.; Desviat L.R.; Merinero B.; Ugarte M.; Perez B.;
Mol. Genet. Metab. 84:317-325(2005)
Cited for: VARIANTS MMAM ARG-109; GLU-191; TYR-219; THR-324; PRO-328; CYS-616 AND ARG-617; VARIANT VAL-69;

Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype.
Worgan L.C.; Niles K.; Tirone J.C.; Hofmann A.; Verner A.; Sammak A.; Kucic T.; Lepage P.; Rosenblatt D.S.;
Hum. Mutat. 27:31-43(2006)
Cited for: VARIANTS MMAM LEU-86; GLU-87; HIS-93; ARG-94; VAL-94; ARG-95; ARG-105; CYS-108; GLY-108; HIS-108; SER-145; SER-174; VAL-186; LYS-189; GLU-191; GLU-197; ARG-203; CYS-215; SER-215; HIS-218; TYR-219; GLN-228; ILE-230; ASN-231; ASN-262; TYR-265; SER-281; GLU-291; SER-305; PHE-306; VAL-312; CYS-316; THR-324; LEU-346 DEL; ARG-347; TYR-350; CYS-369; HIS-369; PRO-370; GLU-377; HIS-383; PRO-383; ARG-386; ASN-386; HIS-388; SER-389 DEL; ILE-412 DEL; ARG-426; ASP-427; PRO-518; TYR-560; ARG-566; SER-573; ARG-615; CYS-616; ARG-623; GLU-630; GLY-633; ARG-637; ARG-642; ARG-678; ARG-685; TRP-694; LYS-700; ARG-703 AND VAL-717; VARIANTS VAL-69; THR-499; HIS-532 AND VAL-671;

Mutation and biochemical analysis of 19 probands with mut0 and 13 with mut- methylmalonic aciduria: identification of seven novel mutations.
Lempp T.J.; Suormala T.; Siegenthaler R.; Baumgartner E.R.; Fowler B.; Steinmann B.; Baumgartner M.R.;
Mol. Genet. Metab. 90:284-290(2007)
Cited for: VARIANTS MMAM CYS-100; HIS-108; VAL-137; TYR-143; LEU-148; GLU-191; ARG-203; HIS-218; TYR-219; ASN-231; PRO-288; PHE-328; PHE-344; SER-366; HIS-369; GLU-454; THR-615; GLU-630; GLY-633; LEU-694; TRP-694 AND LYS-700;

Methylmalonic acidaemia: examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group.
Merinero B.; Perez B.; Perez-Cerda C.; Rincon A.; Desviat L.R.; Martinez M.A.; Sala P.R.; Garcia M.J.; Aldamiz-Echevarria L.; Campos J.; Cornejo V.; Del Toro M.; Mahfoud A.; Martinez-Pardo M.; Parini R.; Pedron C.; Pena-Quintana L.; Perez M.; Pourfarzam M.; Ugarte M.;
J. Inherit. Metab. Dis. 31:55-66(2008)
Cited for: VARIANTS MMAM 7-GLN--VAL-750 DEL; VAL-69; ARG-109; 152-ARG--VAL-750 DEL; GLU-191; ARG-203; TYR-219; 228-ARG--VAL-750 DEL; ASN-231; THR-324; PRO-328; PRO-358; CYS-369; CYS-616; ARG-617 AND TRP-694;

Microarray based mutational analysis of patients with methylmalonic acidemia: identification of 10 no vel mutations.
Duendar H.; Oezguel R.K.; Guezel-Ozantuerk A.; Dursun A.; Sivri S.; Aliefendioglu D.; Coskun T.; Tokatli A.;
Mol. Genet. Metab. 106:419-423(2012)
Cited for: VARIANTS MMAM GLY-137; TYR-219; SER-305; PHE-328; ILE-387; GLU-454; GLU-514; LEU-615; THR-615; VAL-625 AND PHE-674; VARIANTS THR-499; HIS-532 AND VAL-671;

Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.
Forny P.; Froese D.S.; Suormala T.; Yue W.W.; Baumgartner M.R.;
Hum. Mutat. 35:1449-1458(2014)
Cited for: CHARACTERIZATION OF VARIANTS MMAM LEU-86; CYS-100; GLU-191; HIS-218; TYR-219; ASN-231; CYS-316; PHE-328; PHE-344; SER-366; HIS-369; ILE-387; ARG-426; SER-573; LEU-615; THR-615; GLY-633; ASP-648; LEU-694; TRP-694; LYS-700; VAL-717 AND PHE-736; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.