Variant position:  273

Type of variant:  Disease [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

Residue change:  From Arginine (R) to Leucine (L) at position 273 (R273L, p.Arg273Leu).

Physico-chemical properties:  Change from large size and basic (R) to medium size and hydrophobic (L)

BLOSUM score:  -2

Involvement in disease:  Li-Fraumeni syndrome (LFS) [MIM:151623]: An autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. {ECO:0000269|PubMed:10484981, ECO:0000269|PubMed:1565144, ECO:0000269|PubMed:1737852, ECO:0000269|PubMed:1933902, ECO:0000269|PubMed:1978757, ECO:0000269|PubMed:2259385, ECO:0000269|PubMed:7887414, ECO:0000269|PubMed:8825920, ECO:0000269|PubMed:9452042}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Variant description:  In LFS; germline mutation and in sporadic cancers; somatic mutation.

Other resources:  

• Variant rs28934576 [ dbSNP | Ensembl ]

Variant position:  273

Protein sequence length:  393

Location on the sequence:   TIITLEDSSGNLLGRNSFEV  R VCACPGRDRRTEEENLRKKG

Residue conservation: 

Human                         TIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKG

                              TIITLEDSSGNVLGRNSFEVRVCACPGRDRRTEEENFHKKG

Rhesus macaque                TIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENFRKKG

Mouse                         TIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKE

Rat                           TIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKE

Pig                           TIITLEDASGNLLGRNSFEVRVCACPGRDRRTEEENFLKKG

Bovine                        TIITLEDSCGNLLGRNSFEVRVCACPGRDRRTEEENLRKKG

Rabbit                        TIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENFRKKG

Sheep                         TIITLEDSRGNLLGRSSFEVRVCACPGRDRRTEEENFRKKG

Cat                           TIITLEDSNGKLLGRNSFEVRVCACPGRDRRTEEENFRKKG

Chicken                       TILTLEGPGGQLLGRRCFEVRVCACPGRDRKIEEENFRKRG

Xenopus laevis                TIITLETPQGLLLGRRCFEVRVCACPGRDRRTEEDNYTKKR

Zebrafish                     TIITLETQEGQLLGRRSFEVRVCACPGRDRKTEESNFKKDQ

Sequence annotation in neighborhood:  

The consensus coding sequences of human breast and colorectal cancers.
Sjoeblom T.; Jones S.; Wood L.D.; Parsons D.W.; Lin J.; Barber T.D.; Mandelker D.; Leary R.J.; Ptak J.; Silliman N.; Szabo S.; Buckhaults P.; Farrell C.; Meeh P.; Markowitz S.D.; Willis J.; Dawson D.; Willson J.K.V.; Gazdar A.F.; Hartigan J.; Wu L.; Liu C.; Parmigiani G.; Park B.H.; Bachman K.E.; Papadopoulos N.; Vogelstein B.; Kinzler K.W.; Velculescu V.E.;
Science 314:268-274(2006)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-134; PHE-157; CYS-163; HIS-175; ARG-177; ARG-193; PRO-213; PHE-241; PHE-242; GLN-248; TRP-248; SER-249; TRP-267; LYS-271; CYS-273; HIS-273; LEU-273; SER-278; ILE-280 AND HIS-281;