UniProtKB/Swiss-Prot P38398: Variant p.Thr1685Ile

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

1685 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Threonine (T) to Isoleucine (I) at position 1685 (T1685I, p.Thr1685Ile). 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 medium size and polar (T) to medium size and hydrophobic (I) 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
Variant description:

Probable risk factor for cancer; multifactorial likelihood analysis provides evidence for oncogenicity. Any additional useful information about the variant.

Sequence information Variant position:

1685 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:

VYKFARKHHITLTNLITEET T HVVMKTDAEFVCERTLKYFL 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                         VYKFARKHHITLTNLITEETTH-VVMKTDAEFVCERTLKYFL

Gorilla                       VYKFARKHHITLTNLITEETTH-VVMKTDAEFVCERTLKYF

                              VHKFARKHHISLTNLISEETTH-VIMKTDAEFVCERTLKYF

Rhesus macaque                VYKFARRYHIALTNLISEETTH-VVMKTDAEFVCERTLKYF

Chimpanzee                    VYKFARKHHITLTNLITEETTH-VVMKTDAEFVCERTLKYF

Mouse                         VQKFAEKYRLTLTDAITEETTH-VIIKTDAEFVCERTLKYF

Rat                           VQKFAEKYRLALTDVITEETTH-VIIKTDAEFVCERTLKYF

Bovine                        VQKFARKHHVTLTNLITEETTH-VIMKTDPEFVCERTLKYF

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

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	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.
Mutagenesis	1700 – 1700	T -> A. Strongly reduces affinity for a BRIP1 phosphopeptide.
Mutagenesis	1702 – 1702	K -> M. Abolishes interaction with BRIP1.

Literature citations
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; ILE-1685; ALA-1685; ARG-1689; TRP-1699; GLU-1706; GLU-1708; ARG-1715; ARG-1738; PRO-1764; SER-1766 AND VAL-1788; VARIANT BROVCA1 GLY-1623; Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence variants encoding missense substitutions: implications for prediction of pathogenicity.
Walker L.C.; Whiley P.J.; Couch F.J.; Farrugia D.J.; Healey S.; Eccles D.M.; Lin F.; Butler S.A.; Goff S.A.; Thompson B.A.; Lakhani S.R.; Da Silva L.M.; Tavtigian S.V.; Goldgar D.E.; Brown M.A.; Spurdle A.B.;
Hum. Mutat. 31:E1484-E1505(2010)
Cited for: CHARACTERIZATION OF VARIANT ILE-1685; CHARACTERIZATION OF VARIANT BROVCA1 GLY-1623;

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.