UniProtKB/Swiss-Prot Q14524: Variant p.Arg1512Trp

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

1512 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 Arginine (R) to Tryptophan (W) at position 1512 (R1512W, p.Arg1512Trp). 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 large size and basic (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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 BRGDA1; significantly affects cardiac sodium channel characteristics; associated with an increase in inward sodium current during the action potential upstroke. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs137854602 [ dbSNP | Ensembl ]

Sequence information Variant position:

1512 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:

KKYYNAMKKLGSKKPQKPIP R PLNKYQGFIFDIVTKQAFDV 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                         KKYYNAMKKLGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDV

Mouse                         KKYYNAMKKLGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDV

Rat                           KKYYNAMKKLGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDV

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.

Type	Positions	Description
Chain	1 – 2016	Sodium channel protein type 5 subunit alpha
Topological domain	1471 – 1528	Cytoplasmic
Repeat	1510 – 1807	IV
Modified residue	1503 – 1503	Phosphoserine; by PKC

Literature citations
Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome.
Rook M.B.; Bezzina Alshinawi C.; Groenewegen W.A.; van Gelder I.C.; van Ginneken A.C.G.; Jongsma H.J.; Mannens M.M.A.M.; Wilde A.A.M.;
Cardiovasc. Res. 44:507-517(1999)
Cited for: CHARACTERIZATION OF VARIANTS BRGDA1 TRP-1512 AND THR-1924; Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients.
Smits J.P.P.; Eckardt L.; Probst V.; Bezzina C.R.; Schott J.-J.; Remme C.A.; Haverkamp W.; Breithardt G.; Escande D.; Schulze-Bahr E.; LeMarec H.; Wilde A.A.M.;
J. Am. Coll. Cardiol. 40:350-356(2002)
Cited for: VARIANTS BRGDA1 LYS-161; CYS-367; LYS-369; ARG-752; LYS-1225; VAL-1319; ILE-1382; LEU-1405; ARG-1406; LYS-1479 DEL; SER-1502; TRP-1512; GLU-1743 AND THR-1924; 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; 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; LEU-216; 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.