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UniProtKB/Swiss-Prot P38398: Variant p.Phe1226Leu

Breast cancer type 1 susceptibility protein
Gene: BRCA1
Variant information

Variant position:  1226
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Phenylalanine (F) to Leucine (L) at position 1226 (F1226L, p.Phe1226Leu).
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 aromatic (F) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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

Involvement in disease:  Breast-ovarian cancer, familial, 1 (BROVCA1) [MIM:604370]: A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. {ECO:0000269|PubMed:12938098, ECO:0000269|PubMed:14722926, ECO:0000269|PubMed:28364669, ECO:0000269|PubMed:8968716}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In BROVCA1.
Any additional useful information about the variant.



Sequence information

Variant position:  1226
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:   AKKLESSEENLSSEDEELPC  F QHLLFGKVNNIPSQSTRHST
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                         AKKLESSEENLSSEDEELPCFQHLLFGKVNNIPSQSTRHST

Gorilla                       AKKLESSEENLSSEDEELPCFQHLLFGKVSNIPSQSTRHST

                              TKKLESSEENMSSEEEELPCFQHLIFGKVTNMPSQSTSHNA

Rhesus macaque                AKKLESSEENLSSEDEELPCFQHLLFGKVSNIPSQTTRHST

Chimpanzee                    AKKLESSEENLSSEDEELPCFQHLLFGKVSNIPSQSTRHST

Mouse                         SRKLESSEESDSTEDEDLPCFQHLL-SRISNTP-ELTRCSS

Rat                           SRKLEFSEESDSTEDEDLPCFQHLL-SRVSSTP-ELTRCSS

Bovine                        AGKLE-SEETVSSEDEELPCFQQLLFGKVTSTLSPSTGCNT

Caenorhabditis elegans        --------QKLAQKPEVFKSTQNLI----------------

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.

TypePositionsDescription
Chain 1 – 1863 Breast cancer type 1 susceptibility protein
Modified residue 1211 – 1211 Phosphoserine
Modified residue 1217 – 1217 Phosphoserine
Modified residue 1218 – 1218 Phosphoserine
Alternative sequence 64 – 1863 Missing. In isoform 2.
Alternative sequence 224 – 1365 Missing. In isoform 5.
Alternative sequence 264 – 1366 Missing. In isoform 3 and isoform 6.
Mutagenesis 1239 – 1239 S -> A. No effect on in vitro phosphorylation by ATR.


Literature citations

Novel germline mutations in the BRCA1 and BRCA2 genes in Indian breast and breast-ovarian cancer families.
Valarmathi M.T.; Sawhney M.; Deo S.S.V.; Shukla N.K.; Das S.N.;
Hum. Mutat. 23:205-205(2004)
Cited for: VARIANTS BC/BROVCA1 LYS-10; LYS-23; ILE-1187; HIS-1200 AND TYR-1217; VARIANTS BC ILE-1204 AND ASN-1207; VARIANTS BROVCA1 LEU-1226 AND GLY-1243; VARIANT ARG-1183;

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.