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UniProtKB/Swiss-Prot P35555: Variant p.Ile1048Thr

Gene: FBN1
Variant information

Variant position:  1048
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 Isoleucine (I) to Threonine (T) at position 1048 (I1048T, p.Ile1048Thr).
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 hydrophobic (I) to medium size and polar (T)
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:  Marfan syndrome (MFS) [MIM:154700]: A hereditary disorder of connective tissue that affects the skeletal, ocular, and cardiovascular systems. A wide variety of skeletal abnormalities occurs with Marfan syndrome, including scoliosis, chest wall deformity, tall stature, abnormal joint mobility. Ectopia lentis occurs in most of the patients and is almost always bilateral. The leading cause of premature death is progressive dilation of the aortic root and ascending aorta, causing aortic incompetence and dissection. Neonatal Marfan syndrome is the most severe form resulting in death from cardiorespiratory failure in the first few years of life. {ECO:0000269|PubMed:10425041, ECO:0000269|PubMed:10441597, ECO:0000269|PubMed:10694921, ECO:0000269|PubMed:11700157, ECO:0000269|PubMed:11826022, ECO:0000269|PubMed:12161601, ECO:0000269|PubMed:12203992, ECO:0000269|PubMed:12402346, ECO:0000269|PubMed:1301946, ECO:0000269|PubMed:14695540, ECO:0000269|PubMed:15161917, ECO:0000269|PubMed:15221638, ECO:0000269|PubMed:1569206, ECO:0000269|PubMed:16220557, ECO:0000269|PubMed:16222657, ECO:0000269|PubMed:17657824, ECO:0000269|PubMed:18435798, ECO:0000269|PubMed:1852208, ECO:0000269|PubMed:19533785, ECO:0000269|PubMed:19941982, ECO:0000269|PubMed:20803651, ECO:0000269|PubMed:21542060, ECO:0000269|PubMed:22772377, ECO:0000269|PubMed:7611299, ECO:0000269|PubMed:7738200, ECO:0000269|PubMed:7762551, ECO:0000269|PubMed:7870075, ECO:0000269|PubMed:7951214, ECO:0000269|PubMed:7977366, ECO:0000269|PubMed:8004112, ECO:0000269|PubMed:8040326, ECO:0000269|PubMed:8071963, ECO:0000269|PubMed:8136837, ECO:0000269|PubMed:8281141, ECO:0000269|PubMed:8406497, ECO:0000269|PubMed:8504310, ECO:0000269|PubMed:8863159, ECO:0000269|PubMed:8882780, ECO:0000269|PubMed:9016526, ECO:0000269|PubMed:9254848, ECO:0000269|PubMed:9338581, ECO:0000269|PubMed:9401003, ECO:0000269|PubMed:9452085, ECO:0000269|PubMed:9837823, ECO:0000269|Ref.68}. Note=The disease is caused by mutations affecting the gene represented in this entry. The majority of the more than a thousand mutations in FBN1 currently known are point mutations, the rest are frameshifts and splice site mutations. Marfan syndrome has been suggested in at least 2 historical figures, Abraham Lincoln and Paganini.
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 MFS; severe neonatal.
Any additional useful information about the variant.

Sequence information

Variant position:  1048
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2871
The length of the canonical sequence.

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.





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.

Chain 45 – 2731 Fibrillin-1
Domain 1028 – 1069 EGF-like 15; calcium-binding
Glycosylation 1067 – 1067 N-linked (GlcNAc...) asparagine
Disulfide bond 1039 – 1053

Literature citations

Fibrillin-1 mutations in Marfan syndrome and other type-1 fibrillinopathies.
Hayward C.; Brock D.J.H.;
Hum. Mutat. 10:415-423(1997)
Cited for: VARIANTS MFS ARG-996; THR-1048; THR-1048 DEL; CYS-1058 INS; TRP-1086; SER-1837 AND CYS-2680;

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;

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.