Variant information:

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Variant position: 674

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

Type of variant: Polymorphism

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

• Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
• Polymorphism: No disease-association has been reported.
• Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change: From Valine (V) to Isoleucine (I) at position 674 (V674I, p.Val674Ile).

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

Variant description: Slightly increased autophosphorylation.

Any additional useful information about the variant.

Other resources: 

Links to websites of interest for the variant.

• GeneReviews
• NIEHS-SNPs
• Wikipedia; EGFR entry
• Variant rs17337079 [ dbSNP | Ensembl ]

Sequence information:

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Variant position: 674

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

Protein sequence length: 1210

The length of the canonical sequence.

Location on the sequence:  LLLLLVVALGIGLFMRRRHI  V RKRTLRRLLQERELVEPLTP

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                         LLLLLVVALGIGLFMRRRHIVRKRTLRRL---LQERELVEPLTP

Mouse                         LLFIVVVALGIGLFMRRRHIVRKRTLRRL---LQERELVEP

Drosophila                    VLVPTICILCVVTYICRQKQKAKKETVKMTMALSGCEDSEP

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	25 – 1210	Epidermal growth factor receptor
Topological domain	669 – 1210	Cytoplasmic
Modified residue	678 – 678	Phosphothreonine; by PKC and PKD/PRKD1
Modified residue	693 – 693	Phosphothreonine; by PKD/PRKD1
Alternative sequence	406 – 1210	Missing. In isoform 2.
Alternative sequence	628 – 705	CTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLR -> PGNESLKAMLFCLFKLSSCNQSNDGSVSHQSGSPAAQESCLGWIPSLLPSEFQLGWGGCSHLHAWPSASVIITASSCH. In isoform 3.
Alternative sequence	629 – 1210	Missing. In isoform 4.
Mutagenesis	688 – 688	L -> A. Strongly reduced phosphorylation.
Mutagenesis	689 – 689	V -> A. Reduced autophosphorylation.
Mutagenesis	689 – 689	V -> M. Constitutively activated kinase.
Mutagenesis	690 – 690	E -> A. Reduced phosphorylation.
Mutagenesis	692 – 692	L -> AP. Strongly reduced phosphorylation.
Mutagenesis	693 – 693	T -> A. Increased phosphorylation.
Mutagenesis	693 – 693	T -> D. Strongly reduced phosphorylation.
Mutagenesis	694 – 694	P -> A. Strongly reduced phosphorylation.

Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS GLN-98; ARG-266; LYS-521; ILE-674; GLY-962 AND PRO-988;