UniProtKB/Swiss-Prot Q9UM47: Variant p.Arg182Cys

Neurogenic locus notch homolog protein 3
Gene: NOTCH3
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Variant information Variant position:

182 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 182 (R182C, p.Arg182Cys). 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 CADASIL1. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs28933697 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

2321 The length of the canonical sequence.
Location on the sequence:

CRVGEPCRHGGTCLNTPGSF R CQCPAGYTGPLCENPAVPCA 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                         CRVGEPCRHGGTCLNTPGSFRCQCPAGYTGPLCENPAVPCA

Mouse                         CRSGTTCRHGGTCLNTPGSFRCQCPLGYTGLLCENPVVPCA

Rat                           CRAGASCRHGGTCINTPGSFHCLCPLGYTGLLCENPIVPCA

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	40 – 2321	Neurogenic locus notch homolog protein 3
Topological domain	40 – 1643	Extracellular
Domain	158 – 195	EGF-like 4; calcium-binding
Disulfide bond	168 – 183

Literature citations
Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients.
Joutel A.; Vahedi K.; Corpechot C.; Troesch A.; Chabriat H.; Vayssiere C.; Cruaud C.; Maciazek J.; Weissenbach J.; Bousser M.-G.; Bach J.-F.; Tournier-Lasserve E.;
Lancet 350:1511-1515(1997)
Cited for: VARIANTS CADASIL1 TYR-49; CYS-71; CYS-90; CYS-110; CYS-133; CYS-141; ARG-146; CYS-153; CYS-169; CYS-171; CYS-182; ARG-185; SER-212; GLY-222; TYR-224; CYS-258; TYR-542; CYS-558; CYS-578; CYS-728; CYS-985; CYS-1006; CYS-1031; CYS-1231 AND ARG-1261; VARIANTS ARG-170; LEU-496; GLN-1133; MET-1183 AND VAL-2223; Quantitative MRI in CADASIL: correlation with disability and cognitive performance.
Dichgans M.; Filippi M.; Bruening R.; Iannucci G.; Berchtenbreiter C.; Minicucci L.; Uttner I.; Crispin A.; Ludwig H.; Gasser T.; Yousry T.A.;
Neurology 52:1361-1367(1999)
Cited for: VARIANTS CADASIL1 CYS-90; PHE-117; CYS-133; CYS-141; CYS-169; TYR-174; CYS-182 AND ARG-183; Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in Dutch patients. Dutch CADASIL Research Group.
Lesnik Oberstein S.A.J.; Ferrari M.D.; Bakker E.; van Gestel J.; Kneppers A.L.J.; Frants R.R.; Breuning M.H.; Haan J.;
Neurology 52:1913-1915(1999)
Cited for: VARIANTS CADASIL1 CYS-133; CYS-141; CYS-153; CYS-182; CYS-207; CYS-544 AND ARG-1015; Small in-frame deletions and missense mutations in CADASIL: 3D models predict misfolding of Notch3 EGF-like repeat domains.
Dichgans M.; Ludwig H.; Mueller-Hoecker J.; Messerschmidt A.; Gasser T.;
Eur. J. Hum. Genet. 8:280-285(2000)
Cited for: VARIANTS CADASIL1 80-ASP--SER-84 DEL; CYS-90; PHE-93; CYS-110; PHE-117; PHE-123; CYS-133; CYS-141; SER-144; TYR-144; CYS-150; 153-ARG--CYS-155 DEL; CYS-153; CYS-169; TYR-174; CYS-182; ARG-183; SER-183; ARG-185 AND PHE-194; Evaluation of DHPLC analysis in mutational scanning of Notch3, a gene with a high G-C content.
Escary J.-L.; Cecillon M.; Maciazek J.; Lathrop M.; Tournier-Lasserve E.; Joutel A.;
Hum. Mutat. 16:518-526(2000)
Cited for: VARIANTS CADASIL1 TYR-49; CYS-54; CYS-90; CYS-110; 114-GLY--PRO-120 DEL; TYR-123; CYS-133; CYS-141; ARG-146; CYS-153; SER-162; CYS-169; TYR-174; CYS-180; CYS-182; ARG-185; TYR-194; TYR-206; CYS-207; SER-212; GLY-222; TYR-224; CYS-258; TYR-542; CYS-558; CYS-578; CYS-607; CYS-728; CYS-984; CYS-985; CYS-1006; CYS-1031; CYS-1231 AND ARG-1261; Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis.
Joutel A.; Favrole P.; Labauge P.; Chabriat H.; Lescoat C.; Andreux F.; Domenga V.; Cecillon M.; Vahedi K.; Ducros A.; Cave-Riant F.; Bousser M.G.; Tournier-Lasserve E.;
Lancet 358:2049-2051(2001)
Cited for: VARIANTS CADASIL1 CYS-110; CYS-133; TRP-134; CYS-141; CYS-153; CYS-182; GLY-185; CYS-207; SER-212; GLY-222; SER-428; CYS-558; CYS-985 AND CYS-1063; The influence of genetic and cardiovascular risk factors on the CADASIL phenotype.
Singhal S.; Bevan S.; Barrick T.; Rich P.; Markus H.S.;
Brain 127:2031-2038(2004)
Cited for: VARIANTS CADASIL1 ARG-76; CYS-90; CYS-110; CYS-141; CYS-153; CYS-169; CYS-182; ARG-183; CYS-189; SER-194; CYS-207; ARG-251; CYS-332; GLY-440; CYS-607; CYS-953 AND CYS-1231; Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients.
Opherk C.; Peters N.; Herzog J.; Luedtke R.; Dichgans M.;
Brain 127:2533-2539(2004)
Cited for: VARIANTS CADASIL1 GLY-43; PHE-49; CYS-60; SER-65; TRP-76; 77-GLN--CYS-82 DEL; 80-ASP--SER-84 DEL; ARG-87; TYR-87; CYS-90; PHE-93; TRP-106; TYR-108; CYS-110; PHE-117; PHE-123; CYS-133; TRP-134; CYS-141; SER-144; TYR-144; CYS-145; CYS-149; CYS-150; 153-ARG--CYS-155 DEL; CYS-153; SER-155; CYS-169; ARG-174; TYR-174; CYS-182; ARG-183; SER-183; PHE-183; ARG-185; PHE-194; TYR-201; CYS-207; TYR-233; 239-ASP--ASP-253 DEL; SER-240; ARG-245; TYR-260; CYS-332; CYS-335; CYS-337; SER-379; ARG-395; CYS-421; TYR-428; ARG-440; SER-446; TYR-484; TYR-495; ARG-511; TYR-549; CYS-558; CYS-985 AND TYR-1261; Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies.
Peters N.; Opherk C.; Bergmann T.; Castro M.; Herzog J.; Dichgans M.;
Arch. Neurol. 62:1091-1094(2005)
Cited for: VARIANTS CADASIL1 GLY-43; PHE-49; CYS-60; SER-65; TRP-76; 80-ASP--SER-84 DEL; ARG-87; CYS-90; PHE-93; TYR-108; CYS-110; PHE-117; PHE-123; CYS-133; TRP-134; CYS-141; SER-144; TYR-144; CYS-149; CYS-150; CYS-153; 153-ARG--CYS-155 DEL; CYS-169; ARG-174; TYR-174; CYS-182; SER-183; PHE-183; ARG-185; PHE-194; CYS-207; TYR-233; SER-240; ARG-245; TYR-260; 239-ASP--ASP-253 DEL; CYS-319; CYS-332; CYS-335; CYS-337; SER-379; ARG-395; CYS-421; TYR-428; ARG-440; PHE-484; TYR-495; ARG-511; TYR-549; CYS-558; CYS-728; SER-775; CYS-985 AND TYR-1261;

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.