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UniProtKB/Swiss-Prot Q14524: Variant p.Asp1275Asn

Sodium channel protein type 5 subunit alpha
Gene: SCN5A
Chromosomal location: 3p21
Variant information

Variant position:  1275
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 Aspartate (D) to Asparagine (N) at position 1275 (D1275N, p.Asp1275Asn).
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 acidic (D) to medium size and polar (N)
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:  Cardiomyopathy, dilated 1E (CMD1E) [MIM:601154]: 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:15466643, 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.

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.

Involvement in disease:  Atrial standstill 1 (ATRST1) [MIM:108770]: A rare arrhythmia characterized by the absence of electrical and mechanical activity in the atria. Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex escape rhythm. {ECO:0000269|PubMed:12522116, ECO:0000269|PubMed:23420830}. Note=The disease may be caused by mutations affecting distinct genetic loci, including the gene represented in this entry. A mutation in SCN5A has been detected in combination with a rare GJA5 genotype in a large family with atrial standstill.
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:  Brugada syndrome 1 (BRGDA1) [MIM:601144]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:10532948, ECO:0000269|PubMed:10618304, ECO:0000269|PubMed:10690282, ECO:0000269|PubMed:11410597, ECO:0000269|PubMed:11748104, ECO:0000269|PubMed:11823453, ECO:0000269|PubMed:11901046, ECO:0000269|PubMed:12051963, ECO:0000269|PubMed:12106943, ECO:0000269|PubMed:15023552, ECO:0000269|PubMed:15338453, ECO:0000269|PubMed:15579534, ECO:0000269|PubMed:15851320, ECO:0000269|PubMed:16266370, ECO:0000269|PubMed:16325048, ECO:0000269|PubMed:16616735, ECO:0000269|PubMed:17075016, ECO:0000269|PubMed:17081365, ECO:0000269|PubMed:17198989, ECO:0000269|PubMed:18252757, ECO:0000269|PubMed:18341814, ECO:0000269|PubMed:18451998, ECO:0000269|PubMed:18456723, ECO:0000269|PubMed:18616619, ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:19272188, ECO:0000269|PubMed:20129283, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26776555, ECO:0000269|PubMed:9521325}. 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 CMD1E, BRGDA1, PFHB1A and ATRST1; in familial atrial standstill is found in association with polymorphisms in the regulatory region of GJA5; decreases expression at the cell membrane; alters channel kinetics; shifts activation and inactivation to more positive membrane potentials.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1275
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:   LLKWVAYGFKKYFTNAWCWL  D FLIVDVSLVSLVANTLGFAE
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                         LLKWVAYGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAE

Mouse                         LLKWVAYGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAE

Rat                           LLKWVAYGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAE

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
Transmembrane 1271 – 1289 Helical; Name=S3 of repeat III
Repeat 1187 – 1501 III


Literature citations

MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada syndrome and sick sinus syndrome.
Chakrabarti S.; Wu X.; Yang Z.; Wu L.; Yong S.L.; Zhang C.; Hu K.; Wang Q.K.; Chen Q.;
Circ. Arrhythm. Electrophysiol. 6:392-401(2013)
Cited for: FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT ATRST1 ASN-1275; VARIANT ASN-1275 BRGDA1; VARIANT ASN-1275 CMD1E; VARIANT PFHB1A ASN-1275 AND VARIANT BRGDA1 ARG-1743;

A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill.
Groenewegen W.A.; Firouzi M.; Bezzina C.R.; Vliex S.; van Langen I.M.; Sandkuijl L.; Smits J.P.; Hulsbeek M.; Rook M.B.; Jongsma H.J.; Wilde A.A.M.;
Circ. Res. 92:14-22(2003)
Cited for: VARIANT ATRST1 ASN-1275;

SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia.
McNair W.P.; Ku L.; Taylor M.R.G.; Fain P.R.; Dao D.; Wolfel E.; Mestroni L.;
Circulation 110:2163-2167(2004)
Cited for: VARIANT CMD1E ASN-1275;

Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies.
Meregalli P.G.; Tan H.L.; Probst V.; Koopmann T.T.; Tanck M.W.; Bhuiyan Z.A.; Sacher F.; Kyndt F.; Schott J.-J.; Albuisson J.; Mabo P.; Bezzina C.R.; Le Marec H.; Wilde A.A.M.;
Heart Rhythm 6:341-348(2009)
Cited for: VARIANTS BRGDA1 LYS-161; CYS-367; HIS-367; CYS-514; ARG-752; TRP-1232; ASN-1275; VAL-1319; ARG-1408; TRP-1512; GLY-1714; ARG-1740; GLU-1743 AND THR-1924; VARIANTS PFHB1A LYS-161; CYS-367; HIS-367; CYS-514; ARG-752; TRP-1232; ASN-1275; VAL-1319; ARG-1408; TRP-1512; GLY-1714; ARG-1740; GLU-1743 AND THR-1924;

An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.
Kapplinger J.D.; Tester D.J.; Alders M.; Benito B.; Berthet M.; Brugada J.; Brugada P.; Fressart V.; Guerchicoff A.; Harris-Kerr C.; Kamakura S.; Kyndt F.; Koopmann T.T.; Miyamoto Y.; Pfeiffer R.; Pollevick G.D.; Probst V.; Zumhagen S.; Vatta M.; Towbin J.A.; Shimizu W.; Schulze-Bahr E.; Antzelevitch C.; Salisbury B.A.; Guicheney P.; Wilde A.A.; Brugada R.; Schott J.J.; Ackerman M.J.;
Heart Rhythm 7:33-46(2010)
Cited for: VARIANTS TRP-18; CYS-34; HIS-34; LEU-216; SER-286; SER-291; MET-299; CYS-376; GLY-447; ALA-449; VAL-461; SER-475; TRP-481; TYR-524; ARG-558; HIS-568; ARG-579; LYS-592; GLY-596; ALA-601; PHE-618; ASP-638; LEU-656; THR-672; HIS-689; LYS-692; PHE-705; ILE-924; GLN-986; MET-1016; ARG-1040; ALA-1082; LEU-1090; LEU-1098; TYR-1103; LYS-1107; TRP-1116; GLN-1193; MET-1251; SER-1293; PHE-1308; TRP-1512; ASN-1787; THR-1836; LYS-1901; CYS-1919; LEU-1951; GLN-1958; LEU-1962; MET-1968; GLN-1991; LEU-2004 AND ALA-2006; VARIANTS BRGDA1 GLN-18; LYS-70; ASN-84; SER-93; SER-94; GLN-104; TRP-104; LYS-109; GLN-121; TRP-121; GLU-126; PRO-136; MET-146; GLN-161; LYS-161; ASN-175; GLY-178; ARG-182; VAL-185; VAL-204; GLN-212; ILE-220; GLN-222; LEU-223; TRP-225; VAL-226; ILE-232; MET-240; LYS-270; GLN-276; ASP-278; CYS-282; ILE-300; PRO-315; ASN-320; ARG-325; LEU-336; ASP-351; VAL-351; ASN-356; CYS-367; HIS-367; LEU-367; LYS-369; GLY-374; HIS-376; ARG-386; GLU-386; ALA-396; LEU-396; LYS-439; GLY-501; HIS-526; CYS-532; LEU-543; ARG-552; GLU-615; PHE-619; CYS-620; MET-632; ALA-640; ASP-647; LEU-648; TRP-661; GLY-683; LEU-701; LEU-717; VAL-735; LYS-746; ARG-752; GLU-758; ARG-764; ASN-772; SER-773; ILE-789; PRO-808; PRO-839; LEU-851; GLN-867; CYS-878; HIS-878; PRO-886; CYS-893; HIS-893; LYS-901; LEU-910; ARG-915; ARG-917; SER-927; PRO-928; PRO-935; CYS-965; HIS-965; THR-997; LYS-1053; GLY-1055; TYR-1079; VAL-1113; THR-1140; ASN-1219; LYS-1225; HIS-1228; GLN-1232; TRP-1232; PRO-1239; ASN-1243; ASP-1249; GLY-1253; SER-1262; CYS-1271; ASN-1275; GLY-1288; PRO-1311; VAL-1319; GLY-1323; LEU-1332; LEU-1344; ILE-1346; PRO-1346; ARG-1351; MET-1353; TRP-1358; ASN-1359; CYS-1360; TYR-1363; ILE-1382; LEU-1405; MET-1405; ARG-1406; GLU-1406; ARG-1408; CYS-1409; PHE-1412; GLU-1419; ARG-1420; SER-1427; VAL-1428; GLY-1432; SER-1432; VAL-1433; LEU-1438; GLN-1441; LEU-1448; THR-1448; CYS-1449; ASP-1451; TYR-1463; PHE-1468; VAL-1501; LYS-1521; MET-1525; LYS-1548; CYS-1571; LYS-1574; PRO-1582; CYS-1583; HIS-1583; MET-1604; LEU-1613; MET-1620; GLN-1623; GLN-1629; GLU-1642; VAL-1660; ARG-1661; ILE-1667; TYR-1672; THR-1680; THR-1698; ARG-1709; MET-1709; SER-1712; GLY-1714; ASP-1722; ARG-1728; TRP-1728; ARG-1740; ARG-1743; GLU-1743; PHE-1764; MET-1779; LYS-1784; GLU-1832; ILE-1861; ASN-1872; LEU-1903; THR-1924; SER-1935; LYS-1938 AND VAL-2004;

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.