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UniProtKB/Swiss-Prot Q14524: Variant p.Thr512Ile

Sodium channel protein type 5 subunit alpha
Gene: SCN5A
Variant information

Variant position:  512
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 Threonine (T) to Isoleucine (I) at position 512 (T512I, p.Thr512Ile).
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 (T) to medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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:  Progressive familial heart block 1A (PFHB1A) [MIM:113900]: A cardiac bundle branch disorder characterized by progressive alteration of cardiac conduction through the His-Purkinje system, with a pattern of a right bundle-branch block and/or left anterior hemiblock occurring individually or together. It leads to complete atrio-ventricular block causing syncope and sudden death. {ECO:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:12574143, ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:23420830}. 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 PFHB1A; voltage-dependent activation and inactivation of the I-512 channel is shifted negatively by 8 to 9 mV and had enhanced slow activation and slower recovery from inactivation commpared to the wild-type channel; the double mutant R-558/I-512 channel shows that R-558 eliminates the negative shift induced by I-512 but only partially restores the kinetic abnormalities.
Any additional useful information about the variant.

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



Sequence information

Variant position:  512
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2016
The length of the canonical sequence.

Location on the sequence:   DRLPKSDSEDGPRAMNHLSL  T RGLSRTSMKPRSSRGSIFTF
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                         DRLPKSDSEDGPRAMNHLSLTRGLSRTSMKPRSSRGSIFTF

Mouse                         DRLPKSDSEDGPRALNQLSLTHGLSRTSMRPRSSRGSIFTF

Rat                           DRLPKSDSEDGPRALNQLSLTHGLSRTSMRPRSSRGSIFTF

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 – 2016 Sodium channel protein type 5 subunit alpha
Topological domain 411 – 717 Cytoplasmic
Modified residue 497 – 497 Phosphoserine
Modified residue 510 – 510 Phosphoserine
Modified residue 513 – 513 Dimethylated arginine; alternate
Modified residue 513 – 513 Omega-N-methylarginine; alternate
Modified residue 526 – 526 Dimethylated arginine; alternate
Modified residue 526 – 526 Omega-N-methylarginine; alternate


Literature citations

A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation.
Viswanathan P.C.; Benson D.W.; Balser J.R.;
J. Clin. Invest. 111:341-346(2003)
Cited for: VARIANT PFHB1A ILE-512; CHARACTERIZATION OF VARIANT PFHB1A ILE-512; VARIANT ARG-558; CHARACTERIZATION OF VARIANT ARG-558;

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.