UniProtKB/SwissProt variant VAR

Variant information

Variant position:

274

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 Glycine (G) to Aspartate (D) at position 274 (G274D, p.Gly274Asp).

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 glycine (G) to medium size and acidic (D)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-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:

In TOF; temperature sensitive mutation; the protein is abnormally glycosylated and retained intracellularly; unable to activate Notch signaling.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28939668 [ dbSNP | Ensembl ]

Sequence information

Variant position:

274

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

Protein sequence length:

1218

The length of the canonical sequence.

Location on the sequence:

QYGWQGLYCDKCIPHPGCVH G ICNEPWQCLCETNWGGQLCD

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                         QYGWQGLYCDKCIPHPGCVHGICNEPWQCLCETNWGGQLCD

Mouse                         QYGWQGLYCDKCIPHPGCVHGTCNEPWQCLCETNWGGQLCD

Rat                           QYGWQGLYCDKCIPHPGCVHGTCNEPWQCLCETNWGGQLCD

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	34 – 1218	Protein jagged-1
Topological domain	34 – 1067	Extracellular
Domain	264 – 294	EGF-like 2; atypical
Disulfide bond	265 – 276
Disulfide bond	271 – 282
Beta strand	273 – 275

Literature citations

Familial tetralogy of Fallot caused by mutation in the Jagged1 gene.
Eldadah Z.A.; Hamosh A.; Biery N.J.; Montgomery R.A.; Duke M.; Elkins R.; Dietz H.C.;
Hum. Mol. Genet. 10:163-169(2001)
Cited for: VARIANT TOF ASP-274;

Conditional JAG1 mutation shows the developing heart is more sensitive than developing liver to JAG1 dosage.
Lu F.; Morrissette J.J.D.; Spinner N.B.;
Am. J. Hum. Genet. 72:1065-1070(2003)
Cited for: CHARACTERIZATION OF VARIANT ASP-274;

Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis.
Bauer R.C.; Laney A.O.; Smith R.; Gerfen J.; Morrissette J.J.; Woyciechowski S.; Garbarini J.; Loomes K.M.; Krantz I.D.; Urban Z.; Gelb B.D.; Goldmuntz E.; Spinner N.B.;
Hum. Mutat. 31:594-601(2010)
Cited for: VARIANTS SER-664; GLN-937 AND GLN-1104; CHARACTERIZATION OF VARIANTS SER-664 AND GLN-937; VARIANT TOF LEU-810; CHARACTERIZATION OF VARIANTS TOF ASP-274 AND LEU-810; CHARACTERIZATION OF VARIANT ALGS1 SER-37; CHARACTERIZATION OF VARIANT DCHE TYR-234; FUNCTION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P78504: Variant p.Gly274Asp