UniProtKB/SwissProt variant VAR

Variant information

Variant position:

71

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 Tryptophan (W) to Cysteine (C) at position 71 (W71C, p.Trp71Cys).

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 aromatic (W) to medium size and polar (C)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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 rs28937321 [ dbSNP | Ensembl ]

Sequence information

Variant position:

71

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:

NGGRCTQLPSREAACLCPPG W VGERCQLEDPCHSGPCAGRG

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                         NGGRCT-QLPSREAACLCPPGWVGERCQLEDPCHSGPCAGRG

Mouse                         NGGRCTHQQPSLEAACLCLPGWVGERCQLEDPCHSGPCAGR

Rat                           NGGRCTHQQPSREAACLCLPGWVGERCQLEDPCHSGPCAGR

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	40 – 77	EGF-like 1
Disulfide bond	67 – 76

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;

Hypomorphic NOTCH3 alleles do not cause CADASIL in humans.
Rutten J.W.; Boon E.M.; Liem M.K.; Dauwerse J.G.; Pont M.J.; Vollebregt E.; Maat-Kievit A.J.; Ginjaar H.B.; Lakeman P.; van Duinen S.G.; Terwindt G.M.; Lesnik Oberstein S.A.;
Hum. Mutat. 34:1486-1489(2013)
Cited for: VARIANT CADASIL1 CYS-710;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UM47: Variant p.Trp71Cys