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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P38398: Variant p.Val1665Met

Breast cancer type 1 susceptibility protein
Gene: BRCA1
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Variant information Variant position: help 1665 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Valine (V) to Methionine (M) at position 1665 (V1665M, p.Val1665Met). 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: help 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: help 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: help 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: help Links to websites of interest for the variant.


Sequence information Variant position: help 1665 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1863 The length of the canonical sequence.
Location on the sequence: help RVNKRMSMVVSGLTPEEFML V YKFARKHHITLTNLITEETT 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         RVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETT

Gorilla                       RVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETT

                              GVNKRISMVASGLTPKEFMLVHKFARKHHISLTNLISEETT

Rhesus macaque                RVNKRMSLVVSGLTPEEFMLVYKFARRYHIALTNLISEETT

Chimpanzee                    RVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETT

Mouse                         RADRDISMVVSGLTPKEVMTVQKFAEKYRLTLTDAITEETT

Rat                           RAERDISMVVSGLTPKEVMIVQKFAEKYRLALTDVITEETT

Bovine                        RSKKRLSMVASGLTPKELMLVQKFARKHHVTLTNLITEETT

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

Sequence annotation in neighborhood: help 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.
TypePositionsDescription
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.
Helix 1659 – 1671



Literature citations
BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families.
Claes K.; Poppe B.; Coene I.; De Paepe A.; Messiaen L.;
Br. J. Cancer 90:1244-1251(2004)
Cited for: VARIANTS ASN-693; ASN-1040; ALA-1060 AND MET-1665;
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.