UniProtKB/Swiss-Prot P38398: Variant p.Arg1443Gly

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

1443 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 Arginine (R) to Glycine (G) at position 1443 (R1443G, p.Arg1443Gly). 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 basic (R) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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:

In BC; uncertain significance; functionally neutral in vitro. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs41293455 [ dbSNP | Ensembl ]

Sequence information Variant position:

1443 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:

SQPSNSYPSIISDSSALEDL R NPEQSTSEKAVLTSQKSSEY 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                         SQPSNSYPSIISDSSALEDLRNPEQSTSEKAVLTSQKSSEY

Gorilla                       SQPSNSYPSIISDSSALEDLRNPEQSTSEKAVLTSQKSSEY

                              SQPSNSSPSLIADSCSPEDLLNPEQNASER-VLTSEKSSDS

Rhesus macaque                SQPSNSYPSIITDSSALEDLRNPEQSTSEKAVLTSQKSSEY

Chimpanzee                    SQPSNSYPSIISDSSALEDLQNPEQSTSEKAVLTSQKSSEY

Mouse                         NQPSGHSPSLLADPCALEDLPDLEPNMSGAAILTSKNINEN

Rat                           SQPSGHPPCLPADPCALEDLPDPEQNRSGTAILTSKNINEN

Bovine                        SQPSHSSASLTADSRGPEHLLNLEQDTSERAILTSEKSRDY

Caenorhabditis elegans        ----------LANVTCATSSTTLDADRTPKAIQDDEDRIDD

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
Region	1440 – 1505	Disordered
Compositional bias	1440 – 1468	Polar residues
Modified residue	1423 – 1423	Phosphoserine; by ATM and ATR
Modified residue	1457 – 1457	Phosphoserine; by ATR; in vitro
Alternative sequence	64 – 1863	Missing. In isoform 2.
Alternative sequence	1453 – 1453	Missing. In isoform 3 and isoform 6.
Alternative sequence	1453 – 1453	A -> DSHIHGQRNNSMFSKRPREHIS. In isoform 7.
Mutagenesis	1423 – 1423	S -> A. Inhibition of the infrared-induced G2 arrest. Reduces phosphorylation by ATR.
Mutagenesis	1457 – 1457	S -> A. Reduces in vitro phosphorylation by ATR.

Literature citations
Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer.
Castilla L.H.; Couch F.J.; Erdos M.R.; Hoskins K.F.; Calzone K.; Garber J.E.; Boyd J.; Lubin M.B.; Deshano M.L.; Brody L.C.; Collins F.S.; Weber B.L.;
Nat. Genet. 8:387-391(1994)
Cited for: VARIANT BC GLY-64; VARIANTS ALA-772; ASN-1040 AND GLY-1443; Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation screening.
Andersen T.I.; Eiken H.G.; Couch F.; Kaada G.; Skrede M.; Johnsen H.; Aloysius T.A.; Tveit K.M.; Tranebjaerg L.; Doerum A.; Moeller P.; Weber B.L.; Boerresen-Dale A.-L.;
Hum. Mutat. 11:166-174(1998)
Cited for: VARIANT BC GLY-64; VARIANTS ALA-772; GLU-820; ASN-1040; GLY-1443; ILE-1512; LEU-1637 AND ILE-1652; 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.