UniProtKB/Swiss-Prot P35555: Variant p.Arg2726Trp

Fibrillin-1
Gene: FBN1
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Variant information Variant position:

2726 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 2726 (R2726W, p.Arg2726Trp). 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:

Found in a patient with Marfan-like syndrome; likely pathogenic; defects in protein processing. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs61746008 [ dbSNP | Ensembl ]

Sequence information Variant position:

2726 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

2871 The length of the canonical sequence.
Location on the sequence:

DDNSLSPEACYECKINGYPK R GRKRRSTNETDASNIEDQSE 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                         DDNSLSPEACYECKINGYPKRGRKRRSTNETDASNIEDQSE

Mouse                         DDNSLSPEACYECKINGYPKRGRKRRSTNETDASDIQDGSE

Pig                           DDNSLSPEACYECKINGYPKRGRKRRSTNETDAFNIEDQPE

Bovine                        DDNSLSPEACYECKINGYPKRGRKRRSANETDASNIEDQPE

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	45 – 2731	Fibrillin-1
Region	1528 – 2731	C-terminal domain
Region	2726 – 2746	Disordered
Modified residue	2709 – 2709	Phosphoserine
Glycosylation	2734 – 2734	N-linked (GlcNAc...) asparagine
Mutagenesis	2728 – 2728	R -> A. Abolishes furin cleavage site, leading to defects in protein processing at the C-terminus.
Mutagenesis	2731 – 2731	R -> K. Abolishes furin cleavage site, leading to defects in protein processing at the C-terminus.
Mutagenesis	2732 – 2732	S -> T. Defects in protein processing at the C-terminus.

Literature citations
Evidence for furin-type activity-mediated C-terminal processing of profibrillin-1 and interference in the processing by certain mutations.
Loennqvist L.; Reinhardt D.; Sakai L.; Peltonen L.;
Hum. Mol. Genet. 7:2039-2044(1998)
Cited for: PROTEIN SEQUENCE OF 2732-2746; PROTEOLYTIC PROCESSING; MUTAGENESIS OF ARG-2728; ARG-2731 AND SER-2732; CHARACTERIZATION OF VARIANT TRP-2726; A mutation in FBN1 disrupts profibrillin processing and results in isolated skeletal features of the Marfan syndrome.
Milewicz D.M.; Grossfield J.; Cao S.-N.; Kielty C.; Covitz W.; Jewett T.;
J. Clin. Invest. 95:2373-2378(1995)
Cited for: VARIANT TRP-2726; CHARACTERIZATION OF VARIANT TRP-2726; INVOLVEMENT IN MFS; The importance of mutation detection in Marfan syndrome and Marfan-related disorders: report of 193 FBN1 mutations.
Comeglio P.; Johnson P.; Arno G.; Brice G.; Evans A.; Aragon-Martin J.; da Silva F.P.; Kiotsekoglou A.; Child A.;
Hum. Mutat. 28:928-928(2007)
Cited for: VARIANTS MFS CYS-122; SER-214; 248-ASP--HIS-2871 DEL; 351-GLN--HIS-2871 DEL; ARG-365; 366-TRP--HIS-2871 DEL; TRP-474; CYS-545; TRP-546; 565-ARG--HIS-2871 DEL; TYR-727; CYS-828; TYR-832; 861-ARG--HIS-2871 DEL; VAL-882; CYS-974; HIS-976; 994-GLU--HIS-2871 DEL; TYR-1032; THR-1048; TYR-1074; ILE-1088; 1125-ARG--HIS-2871 DEL; TYR-1138; 1140-CYS--HIS-2871 DEL; GLY-1158; HIS-1170; ARG-1223; ARG-1249; TYR-1307; ARG-1326; LEU-1346; LYS-1366; TYR-1402; ALA-1424; ASP-1427; ARG-1485; TYR-1528; 1541-ARG--HIS-2871 DEL; ARG-1622; TYR-1720; TYR-1793; VAL-1796; SER-1806; LYS-1811; CYS-1830; PHE-1835; TRP-1847; ASP-1879; ARG-1987; 2053-CYS--HIS-2871 DEL; MET-2118; GLU-2127; ASP-2144; PRO-2145; TYR-2153; THR-2185; 2220-ARG--HIS-2871 DEL; THR-2269; TRP-2274; LYS-2447; ARG-2489; MET-2520; ARG-2536; 2542-GLN--HIS-2871 DEL; VAL-2555; 2571-CYS--HIS-2871 DEL; TYR-2577; THR-2585; LYS-2610 AND ARG-2618; VARIANTS ECTOL1 CYS-63; SER-68; CYS-240; TRP-365; CYS-545; ARG-596; PRO-634; VAL-882; 1086-CYS--HIS-2871 DEL; ASN-1155; ARG-1692 DEL; GLY-2250; CYS-2272; LYS-2447 AND ARG-2448; VARIANTS ASP-127; ARG-160; SER-164; 215-ARG--HIS-2871 DEL; 364-ARG--HIS-2871 DEL; ARG-504; TYR-652; 653-VAL--HIS-2871 DEL; 752-SER--HIS-2871 DEL; CYS-954; 966-GLU--HIS-2871 DEL; 988-TRP--HIS-2871 DEL; GLY-1028; GLY-1406; SER-1633; 1644-ARG--HIS-2871 DEL; PHE-1777; 1796-GLY--HIS-2871 DEL; TYR-1812; SER-1907; HIS-1930; LYS-2105; ASP-2136; 2169-GLU--HIS-2871 DEL; ARG-2195; PRO-2224; 2229-GLU--HIS-2871 DEL; MET-2234; THR-2273; TRP-2289; TYR-2302; TYR-2365; TRP-2470; ILE-2516; SER-2526; PHE-2541; TRP-2554; TRP-2726 AND 2840-LYS--HIS-2871 DEL; FBN1 mutation screening of patients with Marfan syndrome and related disorders: detection of 46 novel FBN1 mutations.
Attanasio M.; Lapini I.; Evangelisti L.; Lucarini L.; Giusti B.; Porciani M.; Fattori R.; Anichini C.; Abbate R.; Gensini G.; Pepe G.;
Clin. Genet. 74:39-46(2008)
Cited for: VARIANTS MFS TYR-123; SER-136; SER-177; TYR-177; SER-214; 348-GLN--HIS-2871 DEL; 429-ARG--HIS-2871 DEL; ARG-488; TYR-576; ARG-582; PHE-623; CYS-635; TYR-684; CYS-721; ARG-816; SER-880; GLU-884; TYR-1008; SER-1042; 1125-ARG--HIS-2871 DEL; 1136-TYR--HIS-2871 DEL; TRP-1182; TYR-1265; ARG-1320; 1534-CYS--HIS-2871 DEL; 1539-ARG--HIS-2871 DEL; 1541-ARG--HIS-2871 DEL; GLY-1631; ARG-1672; TYR-1672; GLY-1674; 1735-GLN--HIS-2871 DEL; LYS-1811; ARG-1847; TYR-1860; LYS-1894; TYR-1900; GLY-1934; TRP-1977; 2057-ARG--HIS-2871 DEL; 2062-TYR--HIS-2871 DEL; 2064-LYS--HIS-2871 DEL; TYR-2084; LYS-2130; ARG-2221; TYR-2232; THR-2269; THR-2284; TYR-2470; PRO-2561; LYS-2570; ARG-2577 AND 2694-ARG--HIS-2871 DEL; VARIANTS PRO-39; ARG-937; ALA-1020; TRP-2726 AND 2774-LYS--HIS-2871 DEL;

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.