UniProtKB/Swiss-Prot Q12809: Variant p.Thr613Met

Potassium voltage-gated channel subfamily H member 2
Gene: KCNH2
Chromosomal location: 7q35-q36
Variant information

Variant position:  613
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 Methionine (M) at position 613 (T613M, p.Thr613Met).
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 (M)
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:  Long QT syndrome 2 (LQT2) [MIM:613688]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Deafness is often associated with long QT syndrome type 2. {ECO:0000269|PubMed:10086971, ECO:0000269|PubMed:10187793, ECO:0000269|PubMed:10220144, ECO:0000269|PubMed:10517660, ECO:0000269|PubMed:10735633, ECO:0000269|PubMed:10753933, ECO:0000269|PubMed:10862094, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11170080, ECO:0000269|PubMed:12062363, ECO:0000269|PubMed:12354768, ECO:0000269|PubMed:12442276, ECO:0000269|PubMed:12621127, ECO:0000269|PubMed:15051636, ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:16361248, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:22314138, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:7889573, ECO:0000269|PubMed:8635257, ECO:0000269|PubMed:8877771, ECO:0000269|PubMed:8914737, ECO:0000269|PubMed:9024139, ECO:0000269|PubMed:9452080, ECO:0000269|PubMed:9544837, ECO:0000269|PubMed:9600240, ECO:0000269|PubMed:9693036}. 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 LQT2.
Any additional useful information about the variant.

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



Sequence information

Variant position:  613
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1159
The length of the canonical sequence.

Location on the sequence:   IGKPYNSSGLGGPSIKDKYV  T ALYFTFSSLTSVGFGNVSPN
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.

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 – 1159 Potassium voltage-gated channel subfamily H member 2
Intramembrane 612 – 632 Pore-forming; Name=Segment H5
Glycosylation 598 – 598 N-linked (GlcNAc...) asparagine
Mutagenesis 598 – 598 N -> Q. No effect on cell surface expression, but changes inactivation kinetics; when associated with A-631.
Mutagenesis 629 – 629 N -> Q. Abolishes cell surface expression; has no effect on N-glycosylation.
Mutagenesis 631 – 631 S -> A. No effect on cell surface expression, but changes inactivation kinetics; when associated with Q-598.


Literature citations

Novel KCNQ1 and HERG missense mutations in Dutch long-QT families.
Jongbloed R.J.E.; Wilde A.A.M.; Geelen J.L.M.C.; Doevendans P.; Schaap C.; van Langen I.; van Tintelen J.P.; Cobben J.M.; Beaufort-Krol G.C.M.; Geraedts J.P.M.; Smeets H.J.M.;
Hum. Mutat. 13:301-310(1999)
Cited for: VARIANTS LQT2 PRO-558; CYS-582; SER-604; MET-613 AND LEU-640;

Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects.
Laitinen P.; Fodstad H.; Piippo K.; Swan H.; Toivonen L.; Viitasalo M.; Kaprio J.; Kontula K.;
Hum. Mutat. 15:580-581(2000)
Cited for: VARIANTS LQT2 TRP-176; LEU-451; HIS-569; SER-584; SER-601 AND MET-613; VARIANT THR-897;

Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.
Tester D.J.; Will M.L.; Haglund C.M.; Ackerman M.J.;
Heart Rhythm 2:507-517(2005)
Cited for: VARIANTS LQT2 ILE-26; LEU-29; SER-31; ARG-53; LEU-55; PRO-65; ARG-70; PRO-78; VAL-85; GLN-100; SER-238; TRP-306; LEU-320; CYS-328; CYS-420; MET-421; THR-422; SER-427; TYR-456; TYR-475 DEL; CYS-534; SER-552; THR-561; VAL-561; PRO-562; LEU-571; SER-572; CYS-582; SER-584; ASP-588; ARG-596; SER-604; MET-613; VAL-614; PHE-622; ILE-623; SER-628; VAL-628; ALA-630; SER-633; ILE-635; VAL-640; PHE-641; 671-ALA--THR-675 DEL; LEU-721; TYR-774; TRP-784; ASP-788; CYS-805; ARG-820; MET-822; GLY-837; HIS-887; VAL-913; ARG-925; ILE-983; ILE-996 AND ASP-1036;

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.
Kapplinger J.D.; Tester D.J.; Salisbury B.A.; Carr J.L.; Harris-Kerr C.; Pollevick G.D.; Wilde A.A.; Ackerman M.J.;
Heart Rhythm 6:1297-1303(2009)
Cited for: VARIANTS LQT2 ALA-16; GLY-20; LEU-29; THR-30; THR-32; PHE-41; TYR-45; ASP-53; HIS-54; PRO-57; TRP-64; ARG-70; ASN-70; 72-PRO--ALA-80 DELINS ARG-PRO-VAL; GLN-72; LEU-72; ARG-74; MET-74; PRO-74; VAL-85; PRO-86; GLY-94; GLN-100; TRP-100; ALA-102; TYR-106; ARG-108; SER-114; CYS-125; LEU-141; ALA-149; HIS-164; VAL-218; GLY-242; ASN-259; ASP-277; THR-291; LEU-301; CYS-312; SER-314; ASN-323; CYS-328; ARG-402; MET-421; CYS-427; LEU-431; LEU-440; LEU-451; TYR-466; ASN-473; CYS-475; ILE-476; THR-490; CYS-493; SER-493; ASN-501; TRP-531; CYS-534; LEU-534; SER-552; GLU-558; THR-561; VAL-561; ARG-562; THR-565; ASP-572; SER-572; VAL-572; CYS-582; ARG-584; SER-584; CYS-585; LYS-593; ASP-594; HIS-596; LEU-596; CYS-597; ARG-599; CYS-601; SER-601; SER-604; LEU-605; SER-605; GLY-609; MET-613; VAL-614; CYS-616; ASP-626; SER-628; ILE-629; SER-629; ILE-634; ASP-635; LYS-635; ASP-637; ASN-638; LYS-638 DEL; LEU-644; PHE-644; ILE-645; SER-648; ARG-657; LEU-660; THR-662; PRO-678; TYR-687; PRO-693; VAL-711; PHE-728; VAL-749; ASN-757; TYR-767; ALA-770; TYR-774; LYS-788; 791-ARG--LEU-799 DEL; TRP-791; GLU-806; MET-822; TRP-823; TYR-837; SER-846; CYS-885; CYS-894; LEU-894; ARG-903; LEU-906; VAL-913; GLN-920; TRP-920; GLN-922; ALA-924; GLU-924; ASN-937; GLN-1005; HIS-1007; TRP-1033; MET-1038; PRO-1049; VAL-1066; CYS-1078; LEU-1093 AND VAL-1115;

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.