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UniProtKB/Swiss-Prot P38398: Variant p.Val1378Ile

Breast cancer type 1 susceptibility protein
Gene: BRCA1
Variant information

Variant position:  1378
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Valine (V) to Isoleucine (I) at position 1378 (V1378I, p.Val1378Ile).
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:  3
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 cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:10323242, ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11301010, ECO:0000269|PubMed:12427738, ECO:0000269|PubMed:12442275, ECO:0000269|PubMed:12938098, ECO:0000269|PubMed:14722926, ECO:0000269|PubMed:15133502, ECO:0000269|PubMed:18285836, ECO:0000269|PubMed:21473589, ECO:0000269|PubMed:23867111, ECO:0000269|PubMed:28364669, ECO:0000269|PubMed:7545954, ECO:0000269|PubMed:7894491, ECO:0000269|PubMed:7894493, ECO:0000269|PubMed:7939630, ECO:0000269|PubMed:8554067, ECO:0000269|PubMed:8723683, ECO:0000269|PubMed:8776600, ECO:0000269|PubMed:9482581, ECO:0000269|PubMed:9609997, ECO:0000269|PubMed:9760198}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.
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 BC; unknown pathological significance; functionally neutral in vitro.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  1378
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:   EQSMDSNLGEAASGCESETS  V SEDCSGLSSQSDILTTQQRD
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                         EQSMDSNLGEAASGCESETSVSEDCSGLSSQSDILTTQQRD

Gorilla                       EQSMDSNLGEAASGCESETSVSEDCSGLSSQSDILTTQQRD

                              EQSVDSDLGEVASGYESETSLSEDCSRLSSQSDILTTQQRD

Rhesus macaque                EQSVDSNLGEAASGYESETSVSEDCSRLSSQSEILTTQQRD

Chimpanzee                    EQSMDSNLGEAASGCESETSVSEDCSGLSSQSDILTTQQRD

Mouse                         EDSIIPD--SEASGYESETNLSEDC----SQSDILTTQQRA

Rat                           EDSIIPD--SVASGYESEANLSEDC----SQSDILTTQQRA

Bovine                        EQSVDSDLGEAVSDHVSETSLSEDGVGLSSQSDILTTQQRD

Caenorhabditis elegans        -----------------------------------------

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 1387 – 1387 Phosphoserine; by ATM and ATR
Modified residue 1394 – 1394 Phosphothreonine; by ATR; in vitro
Alternative sequence 64 – 1863 Missing. In isoform 2.
Mutagenesis 1387 – 1387 S -> A. Loss of IR-induced S-phase checkpoint. Reduces in vitro phosphorylation by ATR.
Mutagenesis 1394 – 1394 T -> A. Reduces in vitro phosphorylation by ATR.


Literature citations

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.