UniProtKB/Swiss-Prot P09493: Variant p.Asp175Asn

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 175 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [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.] 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 Aspartate (D) to Asparagine (N) at position 175 (D175N, p.Asp175Asn). 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 medium size and acidic (D) to medium size and polar (N) 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 CMH3; no change in homodimerization; no change in homodimer thermal stability; decreased actin binding; recessive effect in the homodimer; increased calcium-dependent regulation of myosin binding to actin filaments; dominant effect in the homodimer. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs104894503 [ dbSNP | Ensembl ]

Sequence information

Variant position: 175 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 284 The length of the canonical sequence.
Location on the sequence: AEDADRKYEEVARKLVIIES D LERAEERAELSEGKCAELEE 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.
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 – 284	Tropomyosin alpha-1 chain
Coiled coil	1 – 284
Modified residue	174 – 174	Phosphoserine
Modified residue	186 – 186	Phosphoserine
Helix	46 – 209

Literature citations

alpha-Tropomyosin with a D175N or E180G mutation in only one chain differs from tropomyosin with mutations in both chains.
Janco M.; Kalyva A.; Scellini B.; Piroddi N.; Tesi C.; Poggesi C.; Geeves M.A.;
Biochemistry 51:9880-9890(2012)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS CMH3 ASN-175 AND GLY-180; SUBUNIT; Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere.
Thierfelder L.; Watkins H.; Macrae C.; Lamas R.; McKenna W.J.; Vosberg H.-P.; Seidman J.G.; Seidman C.E.;
Cell 77:701-712(1994)
Cited for: VARIANTS CMH3 ASN-175 AND GLY-180; Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with hypertrophic cardiomyopathy.
Nakajima-Taniguchi C.; Matsui H.; Nagata S.; Kishimoto T.; Yamauchi-Takihara K.;
J. Mol. Cell. Cardiol. 27:2053-2058(1995)
Cited for: VARIANTS CMH3 VAL-63 AND ASN-175; Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy.
Watkins H.; McKenna W.J.; Thierfelder L.; Suk H.J.; Anan R.; O'Donoghue A.; Spirito P.; Matsumori A.; Moravec C.S.; Seidman J.G.; Seidman C.E.;
N. Engl. J. Med. 332:1058-1064(1995)
Cited for: VARIANT CMH3 ASN-175; The cardiac beta-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population.
Jaeaeskelaeinen P.; Soranta M.; Miettinen R.; Saarinen L.; Pihlajamaeki J.; Silvennoinen K.; Tikanoja T.; Laakso M.; Kuusisto J.;
J. Am. Coll. Cardiol. 32:1709-1716(1998)
Cited for: VARIANT CMH3 ASN-175;