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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P38398: Variant p.Met18Thr

Breast cancer type 1 susceptibility protein
Gene: BRCA1
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Variant information Variant position: help 18 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Methionine (M) to Threonine (T) at position 18 (M18T, p.Met18Thr). 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 Change from medium size and hydrophobic (M) to medium size and polar (T) 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

Variant description: help In BC; uncertain significance. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 18 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 MDLSALRVEEVQNVINA M QKILECPICLELIKEPVSTK 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                         MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTK

Gorilla                       MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTK

                              MDLSADRVEEVQNVLNAMQKILECPICLELIKEPVSTK

Rhesus macaque                MDLSAVRVEEVQNVINAMQKILECPICLELIKEPVSTK

Chimpanzee                    MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTK

Mouse                         MDLSAVQIQEVQNVLHAMQKILECPICLELIKEPVSTK

Rat                           MDLSAVRIQEVQNVLHAMQKILECPICLELIKEPVSTQ

Bovine                        MDLSADHVEEVQNVLNAMQKILECPICLELIKEPVSTK

Caenorhabditis elegans        MADVALRITE---TVARLQKELKCGICCSTYKDPILST

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
Modified residue 1 – 1 N-acetylmethionine
Alternative sequence 1 – 47 Missing. In isoform 8.
Mutagenesis 26 – 26 I -> A. Disrupts the interaction with E2 enzymes, thereby abolishing the E3 ubiquitin-protein ligase activity.
Mutagenesis 26 – 26 I -> E. No ubiquitination of RBBP8. No restoration RBBP8-mediated focus formation or G2/M checkpoint control upon DNA damage.
Helix 8 – 21



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; 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.