UniProtKB/Swiss-Prot P38398: Variant p.Ser1512Ile

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

1512 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 Serine (S) to Isoleucine (I) at position 1512 (S1512I, p.Ser1512Ile). 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 small size and polar (S) to medium size and hydrophobic (I) 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
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 rs1800744 [ dbSNP | Ensembl ]

Sequence information Variant position:

1512 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:

GVERSSPSKCPSLDDRWYMH S CSGSLQNRNYPSQEELIKVV 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                         GVERSSPSKCPSLDDRWYMHSCSGSLQNRNYPSQEELIKVV

Gorilla                       GVERSSPSKCPSLDDRWYMHSCSGSLQNRNYPSQEELIKVV

                              GMIRSSPSQSRLLDTRWYVHSCPRSLQDTNCPSQKELTKVV

Rhesus macaque                GVERSSPSKCQSLEDRWYVHSSSGSLQNGNYPSQEELIKVV

Chimpanzee                    GVERSSPSKCPSLDDRWYMHSCSGSLQNRNYPSQEELIKVV

Mouse                         GMGRPSPFKSPLAGSRGSAHGCSRHLQKRNSPSQEELLQPA

Rat                           GMRRPSPFKSPLTSSRCSARGHSRSLQNRNSTSQEELLQPA

Bovine                        GMERSSASKFQLSYNRWYMHS-SRSLQDRNCPSQKEPINVA

Caenorhabditis elegans        GLELLSDFYHKFLSNAC------------------------

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
Modified residue	1524 – 1524	Phosphoserine; by ATM
Alternative sequence	64 – 1863	Missing. In isoform 2.
Mutagenesis	1524 – 1524	S -> A. No change in infrared S-phase delay; when associated with A-1387. No effect on in vitro phosphorylation by ATR.

Literature citations
A high proportion of mutations in the BRCA1 gene in German breast/ovarian cancer families with clustering of mutations in the 3' third of the gene.
Dong J.; Chang-Claude J.; Wu Y.; Schumacher V.; Debatin I.; Tonin P.; Royer-Pokora B.;
Hum. Genet. 103:154-161(1998)
Cited for: VARIANT BC GLY-61; VARIANTS ARG-239; TRP-841 AND ILE-1512; 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;

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.