UniProtKB/Swiss-Prot P38398: Variant p.Met1652Ile

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

1652 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 Methionine (M) to Isoleucine (I) at position 1652 (M1652I, p.Met1652Ile). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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
Polymorphism:

There is evidence that the presence of the rare form of Gln-356-Arg and Leu-871-Pro polymorphisms may be associated with an increased risk for developing ovarian cancer. Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs1799967 [ dbSNP | Ensembl ]

Sequence information Variant position:

1652 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:

VSREKPELTASTERVNKRMS M VVSGLTPEEFMLVYKFARKH 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                         VSREKPELTASTERVNKRMSMVVSGLTPEEFMLVYKFARKH

Gorilla                       VSREKPELTASTERVNKRMSMVVSGLTPEEFMLVYKFARKH

                              VGIEKPEVISSTRGVNKRISMVASGLTPKEFMLVHKFARKH

Rhesus macaque                VSRENPKLTASTERVNKRMSLVVSGLTPEEFMLVYKFARRY

Chimpanzee                    VSREKPELTASTERVNKRMSMVVSGLTPEEFMLVYKFARKH

Mouse                         VSKIKPELTSSEERADRDISMVVSGLTPKEVMTVQKFAEKY

Rat                           VSKIKPEVTSPKERAERDISMVVSGLTPKEVMIVQKFAEKY

Bovine                        MSKEKPEVISSTERSKKRLSMVASGLTPKELMLVQKFARKH

Caenorhabditis elegans        -----------------------------------RFAED-

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	1655 – 1655	S -> A. Abolishes interaction with BRIP1.
Mutagenesis	1656 – 1656	G -> D. No effect on affinity for a BRIP1 phosphopeptide.
Mutagenesis	1662 – 1662	F -> S. Does not abolish ABRAXAS1 binding, but abolishes formation of a heterotetramer with ABRAXAS1.
Mutagenesis	1663 – 1663	M -> K. Does not abolish ABRAXAS1 binding, but abolishes formation of a heterotetramer with ABRAXAS1.
Mutagenesis	1666 – 1666	Y -> A. Does not abolish ABRAXAS1 binding, but impairs formation of a heterotetramer with ABRAXAS1.
Mutagenesis	1670 – 1670	R -> E. Impairs formation of a heterotetramer with ABRAXAS1.
Mutagenesis	1671 – 1671	K -> E. Impairs formation of a heterotetramer with ABRAXAS1.
Beta strand	1651 – 1656

Literature citations
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6 AND 7); VARIANTS LEU-871; GLY-1038; ARG-1183; GLY-1613 AND ILE-1652; Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation screening.
Andersen T.I.; Eiken H.G.; Couch F.; Kaada G.; Skrede M.; Johnsen H.; Aloysius T.A.; Tveit K.M.; Tranebjaerg L.; Doerum A.; Moeller P.; Weber B.L.; Boerresen-Dale A.-L.;
Hum. Mutat. 11:166-174(1998)
Cited for: VARIANT BC GLY-64; VARIANTS ALA-772; GLU-820; ASN-1040; GLY-1443; ILE-1512; LEU-1637 AND ILE-1652; Characterization of common BRCA1 and BRCA2 variants.
Deffenbaugh A.M.; Frank T.S.; Hoffman M.; Cannon-Albright L.; Neuhausen S.L.;
Genet. Test. 6:119-121(2002)
Cited for: VARIANTS GLY-1347; ILE-1512 AND ILE-1652; 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;

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.