UniProtKB/Swiss-Prot P38398: Variant p.Arg1699Trp

Breast cancer type 1 susceptibility protein
Gene: BRCA1
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Variant information Variant position:

1699 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 Tryptophan (W) at position 1699 (R1699W, p.Arg1699Trp). 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:

In BC, OC and FANCS; impairs protein stability; functionally impaired in vitro. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs55770810 [ dbSNP | Ensembl ]

Sequence information Variant position:

1699 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1863 The length of the canonical sequence.
Location on the sequence:

LITEETTHVVMKTDAEFVCE R TLKYFLGIAGGKWVVSYFWV 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                         LITEETTH-VVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWV

Gorilla                       LITEETTH-VVMKTDAEFVCERTLKYFLGIAGGKWVVSYFW

                              LISEETTH-VIMKTDAEFVCERTLKYFLGIAGGKWVVSYFW

Rhesus macaque                LISEETTH-VVMKTDAEFVCERTLKYFLGIAGGKWVVSYFW

Chimpanzee                    LITEETTH-VVMKTDAEFVCERTLKYFLGIAGGKWVVSYFW

Mouse                         AITEETTH-VIIKTDAEFVCERTLKYFLGIAGGKWIVSYSW

Rat                           VITEETTH-VIIKTDAEFVCERTLKYFLGIAGGKWIVSYSW

Bovine                        LITEETTH-VIMKTDPEFVCERTLKYFLGIAGGKWVVSYFW

Caenorhabditis elegans        -VNEHTTHLVMMNSEGRSISQKSTAYLYAIARKCVIVGRQW

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 – 1863	Breast cancer type 1 susceptibility protein
Domain	1642 – 1736	BRCT 1
Alternative sequence	64 – 1863	Missing. In isoform 2.
Mutagenesis	1700 – 1700	T -> A. Strongly reduces affinity for a BRIP1 phosphopeptide.
Mutagenesis	1702 – 1702	K -> M. Abolishes interaction with BRIP1.

Literature citations
Impact of BRCA1 BRCT domain missense substitutions on phosphopeptide recognition.
Coquelle N.; Green R.; Glover J.N.;
Biochemistry 50:4579-4589(2011)
Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH PHOSPHORYLATED BRIP1 PEPTIDE; INTERACTION WITH BRIP1; MUTAGENESIS OF GLY-1656; THR-1700; ARG-1835 AND GLU-1836; CHARACTERIZATION OF VARIANTS BC GLN-1699 AND TRP-1699; One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 mutations: results of a prospective study in Southern Sweden.
Malander S.; Ridderheim M.; Masbaeck A.; Loman N.; Kristoffersson U.; Olsson H.; Nilbert M.; Borg A.;
Eur. J. Cancer 40:422-428(2004)
Cited for: VARIANTS OC GLY-61; THR-1411; ARG-1697 AND TRP-1699; A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.
Easton D.F.; Deffenbaugh A.M.; Pruss D.; Frye C.; Wenstrup R.J.; Allen-Brady K.; Tavtigian S.V.; Monteiro A.N.A.; Iversen E.S.; Couch F.J.; Goldgar D.E.;
Am. J. Hum. Genet. 81:873-883(2007)
Cited for: VARIANTS THR-18; MET-1495; ALA-1685; ARG-1689; TRP-1699; GLU-1706; GLU-1708; ARG-1715; ARG-1738; PRO-1764; SER-1766 AND VAL-1788; VARIANTS BROVCA1 GLY-1623 AND ILE-1685; A high-throughput functional complementation assay for classification of BRCA1 missense variants.
Bouwman P.; van der Gulden H.; van der Heijden I.; Drost R.; Klijn C.N.; Prasetyanti P.; Pieterse M.; Wientjens E.; Seibler J.; Hogervorst F.B.; Jonkers J.;
Cancer Discov. 3:1142-1155(2013)
Cited for: CHARACTERIZATION OF VARIANTS BC PHE-4; THR-18; GLN-45; GLY-61; GLY-64; TYR-67; LYS-132; HIS-142; PHE-147; PRO-165; TRP-170; TYR-186; ILE-191; MET-231; VAL-245; VAL-246; LEU-271; PHE-668; ASN-695; LEU-798; TYR-810; LYS-826; GLN-841; HIS-856; ASN-1101; ASN-1140; GLY-1140; LYS-1214; LYS-1236; SER-1267; VAL-1282; SER-1297 DEL; ARG-1301; LYS-1346; ILE-1378; VAL-1400; PRO-1407; THR-1411; GLY-1443; GLY-1448; CYS-1486; MET-1534; PRO-1589; THR-1628; PRO-1651; PHE-1651; PHE-1655; ARG-1686; GLN-1686; VAL-1688 DEL; ILE-1691; TRP-1699; GLN-1699; GLU-1706; ALA-1706; GLU-1708; CYS-1718; ALA-1720; LYS-1735; ALA-1736; GLY-1739; VAL-1739; GLN-1746; THR-1753; PRO-1764; SER-1767; VAL-1770; CYS-1782; THR-1789; ASP-1794; ASP-1804; ARG-1812; ARG-1837 AND LEU-1862; VARIANTS CYS-105; CYS-866; ALA-1060; LYS-1250 AND ILE-1652; Biallelic mutations in BRCA1 cause a new Fanconi anemia subtype.
Sawyer S.L.; Tian L.; Kaehkoenen M.; Schwartzentruber J.; Kircher M.; Majewski J.; Dyment D.A.; Innes A.M.; Boycott K.M.; Moreau L.A.; Moilanen J.S.; Greenberg R.A.;
Cancer Discov. 5:135-142(2015)
Cited for: VARIANT FANCS TRP-1699; SUBCELLULAR LOCATION;

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.