UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1226

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

Type of variant:

LP/P [Disclaimer]

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 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

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.

Type	Positions	Description
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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P38398: Variant p.Phe1226Leu