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UniProtKB/Swiss-Prot P38398: Variant p.Leu1780Pro

Breast cancer type 1 susceptibility protein
Gene: BRCA1
Variant information

Variant position:  1780
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 Leucine (L) to Proline (P) at position 1780 (L1780P, p.Leu1780Pro).
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-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.

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.

Involvement in disease:  Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. {ECO:0000269|PubMed:10196379, ECO:0000269|PubMed:10486320, ECO:0000269|PubMed:14746861, ECO:0000269|PubMed:28364669}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
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, BROVCA1 and OC; unknown pathological significance.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1780
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:   IFRGLEICCYGPFTNMPTDQ  L EWMVQLCGASVVKELSSFTL
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                         IFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVVKELSSFTL

Gorilla                       IFRGLDICCYGPFTNMPTDQLEWMVQL---CGASVVKELSS

                              IFRGLEICCYGPFTNMPTDQLEWMVHL---CGASVVKEPSL

Rhesus macaque                IFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVVKELSS

Chimpanzee                    IFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVVKELSS

Mouse                         LFKGLQVYCCEPFTNMPKDELERMLQL---CGASVVKELPS

Rat                           LFEGLQIYCCEPFTNMPKDELERMLQL---CGASVVKELPL

Bovine                        IFKGLEICCYGPFTNMPTDQLEWMVQL---CGASVVKEPSS

Caenorhabditis elegans        LFAGRRFMILRKFTMNPYFDYKQLIELVQQCGGEILSCYEN

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
Domain 1756 – 1855 BRCT 2
Alternative sequence 64 – 1863 Missing. In isoform 2.
Alternative sequence 1778 – 1863 DQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLIPQIPHSHY -> GCPPNCGCAARCLDRGQWLPCNWADV. In isoform 6.
Helix 1777 – 1786


Literature citations

Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from 'unknown significance' to 'Likely pathogenic' based on clinical evidence in Korea.
Ryu J.M.; Kang G.; Nam S.J.; Kim S.W.; Yu J.; Lee S.K.; Bae S.Y.; Park S.; Paik H.J.; Kim J.W.; Park S.S.; Lee J.E.; Kim S.W.;
Breast 33:109-116(2017)
Cited for: VARIANT BC PRO-1780; VARIANT BROVCA1 PRO-1780; VARIANT OC PRO-1780;

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.