UniProtKB/Swiss-Prot P00451: Variant p.Arg612Cys

Coagulation factor VIII
Gene: F8
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Variant information Variant position:

612 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 Cysteine (C) at position 612 (R612C, p.Arg612Cys). 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 medium size and polar (C) 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 HEMA; mild/moderate; secretion impaired. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs137852428 [ dbSNP | Ensembl ]

Sequence information Variant position:

612 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

2351 The length of the canonical sequence.
Location on the sequence:

VILFSVFDENRSWYLTENIQ R FLPNPAGVQLEDPEFQASNI 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                         VILFSVFDENRSWYLTENIQRFLPNPAGVQLEDPEFQASNI

                              VILFSVFDENRSWYLTENMQRFLPNADVVQPHDPEFQLSNI

Mouse                         VILFSIFDENQSWYITENMQRFLPNAAKTQPQDPGFQASNI

Pig                           VILFSVFDENQSWYLAENIQRFLPNPDGLQPQDPEFQASNI

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	20 – 2351	Coagulation factor VIII
Chain	20 – 1332	Factor VIIIa heavy chain, 200 kDa isoform
Chain	20 – 759	Factor VIIIa heavy chain, 92 kDa isoform
Domain	399 – 730	F5/8 type A 2
Domain	583 – 730	Plastocyanin-like 4
Glycosylation	601 – 601	N-linked (GlcNAc...) asparagine
Alternative sequence	9 – 2143	Missing. In isoform 2.
Helix	606 – 613

Literature citations
Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.
Higuchi M.; Kazazian H.H. Jr.; Kasch L.; Warren T.C.; McGinniss M.J.; Phillips J.A. III; Kasper C.; Janco R.; Antonarakis S.E.;
Proc. Natl. Acad. Sci. U.S.A. 88:7405-7409(1991)
Cited for: VARIANTS HEMA THR-108; VAL-110; GLY-285; HIS-301; SER-312; ARG-444; HIS-492; GLY-561; CYS-612; THR-723; PHE-1699; HIS-1800; TYR-1803; ASP-1941; SER-1941; HIS-2169; GLN-2228 AND CYS-2323; Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.
Diamond C.; Kogan S.; Levinson B.; Gitschier J.;
Hum. Mutat. 1:248-257(1992)
Cited for: VARIANTS HEMA VAL-30; VAL-89; VAL-92; ASP-104; VAL-164; MET-181; CYS-550; GLY-554; CYS-612; TRP-717; PHE-1808; SER-1941; ARG-2065; HIS-2169; CYS-2178 AND CYS-2248; Screening for mutations in haemophilia A patients by multiplex PCR-SSCP, Southern blotting and RNA analysis: the detection of a genetic abnormality in the factor VIII gene in 30 out of 35 patients.
Pieneman W.C.; Deutz-Terlouw P.P.; Reitsma P.H.; Brieet E.;
Br. J. Haematol. 90:442-449(1995)
Cited for: VARIANTS HEMA HIS-217; ILE-299; ASN-450; TRP-546; CYS-612; VAL-705; CYS-1708; TRP-2016 AND ARG-2119; Factor VIII inhibitors in mild and moderate-severity haemophilia A.
Hay C.R.M.; Ludlam C.A.; Colvin B.T.; Hill F.G.H.; Preston F.E.; Wasseem N.; Bagnall R.; Peake I.R.; Berntorp E.; Mauser Bunschoten E.P.; Fijnvandraat K.; Kasper C.K.; White G.; Santagostino E.;
Thromb. Haemost. 79:762-766(1998)
Cited for: VARIANTS HEMA CYS-612; PHE-682; ARG-2028; CYS-2124; HIS-2169; HIS-2182; ASP-2200; CYS-2248 AND ILE-2279; Start of UK confidential haemophilia A database: analysis of 142 patients by solid phase fluorescent chemical cleavage of mismatch.
Waseem N.H.; Bagnall R.; Green P.M.; Giannelli F.;
Thromb. Haemost. 81:900-905(1999)
Cited for: VARIANTS HEMA CYS-24; ARG-26; TYR-113; SER-121; TRP-172; PRO-176; MET-181; VAL-214; THR-219; LYS-291; ALA-314; VAL-315; LYS-340; PHE-405; GLY-412; THR-470; GLU-474; ASN-478; CYS-484; GLY-490; ARG-498; TRP-546; CYS-550; HIS-561; ARG-584; THR-585; GLY-588; ASP-601; LYS-601; GLY-602; HIS-605; CYS-612; TRP-717; CYS-1708; GLN-1751; HIS-1800; CYS-1802; THR-1853; GLU-1864; PRO-1882; ILE-1888; LEU-1973; TRP-2016; ALA-2035; TYR-2040; CYS-2120; CYS-2145; HIS-2169; CYS-2178; HIS-2182; VAL-2183; VAL-2198; CYS-2248 AND GLY-2326; Intracellular accumulation of factor VIII induced by missense mutations Arg593-->Cys and Asn618-->Ser explains cross-reacting material-reduced haemophilia A.
Roelse J.C.; De Laaf R.T.M.; Timmermans S.M.H.; Peters M.; Van Mourik J.A.; Voorberg J.;
Br. J. Haematol. 108:241-246(2000)
Cited for: VARIANTS HEMA CYS-612 AND SER-637; CHARACTERIZATION OF VARIANTS HEMA CYS-612 AND SER-637; Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations.
Timur A.A.; Guergey A.; Aktuglu G.; Kavakli K.; Canatan D.; Olek K.; Caglayan S.H.;
Haemophilia 7:475-481(2001)
Cited for: VARIANTS HEMA ASN-67; PHE-117; ALA-137; TYR-267; CYS-301; HIS-301; TYR-348; LYS-475; ALA-579; CYS-612; CYS-683; LEU-698; TRP-710; CYS-1708; HIS-1788; LEU-1876; TRP-2016; GLU-2045; CYS-2178; CYS-2182; HIS-2182; PRO-2182; ALA-2307 AND LEU-2323; Rapid hemophilia A molecular diagnosis by a simple DNA sequencing procedure: identification of 14 novel mutations.
Vidal F.; Farssac E.; Altisent C.; Puig L.; Gallardo D.;
Thromb. Haemost. 85:580-583(2001)
Cited for: VARIANTS HEMA ARG-193; CYS-391; CYS-550; CYS-612; HIS-1705; ARG-1782; GLU-1872; TRP-2016; PRO-2016; HIS-2169 AND HIS-2182; Non-inversion factor VIII mutations in 80 hemophilia A families including 24 with alloimmune responses.
Liu M.-L.; Nakaya S.; Thompson A.R.;
Thromb. Haemost. 87:273-276(2002)
Cited for: VARIANTS HEMA GLU-67; 84-ARG-PRO-85 DEL; PRO-85 DEL; MET-181; TYR-186; GLY-220; LEU-262; ARG-412; PHE-438; ASP-439; ARG-470; SER-513; SER-541; CYS-550; GLY-554; SER-583; GLN-594; ILE-609; CYS-612; ASN-635; THR-699; ILE-701; ILE-721; ARG-1779; LEU-1780; THR-1791; PRO-1798; HIS-1800; GLY-1848; ARG-1907; CYS-1907; THR-1939; VAL-1939; ILE-1982; GLN-1985; CYS-2015; TRP-2016; SER-2038; HIS-2169; ILE-2192 AND LEU-2326; 11 hemophilia A patients without mutations in the factor VIII encoding gene.
Klopp N.; Oldenburg J.; Uen C.; Schneppenheim R.; Graw J.;
Thromb. Haemost. 88:357-360(2002)
Cited for: VARIANTS HEMA ASP-147; CYS-301; CYS-612; VAL-1945; CYS-2178 AND GLN-2326; VARIANT GLU-1260; Small FVIII gene rearrangements in 18 hemophilia A patients: five novel mutations.
Bicocchi M.P.; Pasino M.; Lanza T.; Bottini F.; Molinari A.C.; Caprino D.; Rosano C.; Acquila M.;
Am. J. Hematol. 78:117-122(2005)
Cited for: VARIANTS HEMA THR-111; ASP-450; CYS-612; HIS-1800; CYS-1802 AND ALA-2251;

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.