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UniProtKB/Swiss-Prot P35609: Variant p.Ala119Thr

Alpha-actinin-2
Gene: ACTN2
Variant information

Variant position:  119
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Alanine (A) to Threonine (T) at position 119 (A119T, p.Ala119Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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

Involvement in disease:  Cardiomyopathy, familial hypertrophic 23, with or without left ventricular non-compaction (CMH23) [MIM:612158]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:20022194, ECO:0000269|PubMed:25173926}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in disease:  Cardiomyopathy, dilated 1AA, with or without left ventricular non-compaction (CMD1AA) [MIM:612158]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:14567970, ECO:0000269|PubMed:25224718}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In CMH23 and CMD1AA.
Any additional useful information about the variant.

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



Sequence information

Variant position:  119
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  894
The length of the canonical sequence.

Location on the sequence:   NVNKALDYIASKGVKLVSIG  A EEIVDGNVKMTLGMIWTIIL
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                         NVNKALDYIASKGVKLVSIGAEEIVDGNVKMTLGMIWTIIL

Mouse                         NVNKALDYIASKGVKLVSIGAEEIVDGNVKMTLGMIWTIIL

Bovine                        NVNKALDYIASKGVKLVSIGAEEIVDGNVKMTLGMIWTIIL

Chicken                       NVNKALDYIASKGVKLVSIGAEEIVDGNVKMTLGMIWTIIL

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 1 – 894 Alpha-actinin-2
Domain 38 – 142 Calponin-homology (CH) 1
Region 1 – 254 Actin-binding
Helix 119 – 123


Literature citations

Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis.
Chiu C.; Bagnall R.D.; Ingles J.; Yeates L.; Kennerson M.; Donald J.A.; Jormakka M.; Lind J.M.; Semsarian C.;
J. Am. Coll. Cardiol. 55:1127-1135(2010)
Cited for: VARIANTS CMH23 THR-119; MET-495; ALA-583 AND GLY-628;

Exome sequencing identifies a mutation in the ACTN2 gene in a family with idiopathic ventricular fibrillation, left ventricular noncompaction, and sudden death.
Bagnall R.D.; Molloy L.K.; Kalman J.M.; Semsarian C.;
BMC Med. Genet. 15:99-99(2014)
Cited for: VARIANT CMD1AA THR-119;

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.