UniProtKB/Swiss-Prot O76090: Variant p.Arg218Cys

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 218 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 218 (R218C, p.Arg218Cys). 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 VMD2. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs281865238 [ dbSNP | Ensembl ]

Sequence information

Variant position: 218 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 585 The length of the canonical sequence.
Location on the sequence: GGRIRDPILLQSLLNEMNTL R TQCGHLYAYDWISIPLVYTQ 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.

Type	Positions	Description
Chain	1 – 585	Bestrophin-1
Topological domain	83 – 237	Cytoplasmic
Mutagenesis	221 – 221	C -> A. Impairs inactivation of ligand-gated anion channel activity by sulfhydryl-reactive agents; when associated with A-23; A-42; A-69 and A-251.
Helix	204 – 229

Literature citations

Bestrophin gene mutations in patients with Best vitelliform macular dystrophy.
Caldwell G.M.; Kakuk L.E.; Griesinger I.B.; Simpson S.A.; Nowak N.J.; Small K.W.; Maumenee I.H.; Rosenfeld P.J.; Sieving P.A.; Shows T.B.; Ayyagari R.;
Genomics 58:98-101(1999)
Cited for: VARIANTS VMD2 HIS-13; CYS-93; CYS-218; ASP-300; GLU-301 AND ILE-307; The mutation spectrum of the bestrophin protein -- functional implications.
Bakall B.; Marknell T.; Ingvast S.; Koisti M.J.; Sandgren O.; Li W.; Bergen A.A.B.; Andreasson S.; Rosenberg T.; Petrukhin K.; Wadelius C.;
Hum. Genet. 104:383-389(1999)
Cited for: VARIANTS VMD2 VAL-10; VAL-82; CYS-92; HIS-96; SER-135; CYS-218; SER-218 AND LYS-293; Allelic variation in the VMD2 gene in best disease and age-related macular degeneration.
Lotery A.J.; Munier F.L.; Fishman G.A.; Weleber R.G.; Jacobson S.G.; Affatigato L.M.; Nichols B.E.; Schorderet D.F.; Sheffield V.C.; Stone E.M.;
Invest. Ophthalmol. Vis. Sci. 41:1291-1296(2000)
Cited for: VARIANTS AGE-RELATED MACULAR DEGENERATION CYS-105 AND ILE-275; VARIANTS VMD2 ARG-6; CYS-17; CYS-24; TRP-25; ARG-30; LEU-80; ILE-91; THR-101; GLN-119; LYS-133; SER-135; ARG-140; HIS-141; VAL-195; THR-201; ILE-207; CYS-218; HIS-218; VAL-222; PRO-224; ASN-227; CYS-227; THR-243; LEU-276; HIS-296; ALA-297; ASP-300; LYS-300; GLY-302; VAL-302; ASP-306; GLY-306; ALA-307 AND ILE-307; Identification of novel VMD2 gene mutations in patients with Best vitelliform macular dystrophy.
Marchant D.; Gogat K.; Boutboul S.; Pequignot M.; Sternberg C.; Dureau P.; Roche O.; Uteza Y.; Hache J.C.; Puech B.; Puech V.; Dumur V.; Mouillon M.; Munier F.L.; Schorderet D.F.; Marsac C.; Dufier J.-L.; Abitbol M.;
Hum. Mutat. 17:235-235(2001)
Cited for: VARIANTS VMD2 PHE-16; CYS-17; ASN-73; HIS-92; CYS-218; HIS-218; LEU-235 AND SER-296; Mutation analysis of the VMD2 gene in Thai families with Best macular dystrophy.
Atchaneeyasakul L.O.; Jinda W.; Sakolsatayadorn N.; Trinavarat A.; Ruangvoravate N.; Thanasombatskul N.; Thongnoppakhun W.; Limwongse C.;
Ophthalmic Genet. 29:139-144(2008)
Cited for: VARIANTS VMD2 CYS-218 AND MET-242;