UniProtKB/SwissProt variant VAR

Variant information

Variant position:

403

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 Arginine (R) to Glutamine (Q) at position 403 (R403Q, p.Arg403Gln).

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 large size and basic (R) to medium size and polar (Q)

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 CMH1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121913624 [ dbSNP | Ensembl ]

Sequence information

Variant position:

403

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

Protein sequence length:

1935

The length of the canonical sequence.

Location on the sequence:

KSAYLMGLNSADLLKGLCHP R VKVGNEYVTKGQNVQQVIYA

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                         KSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQNVQQVIYA

                              KSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQNVQQVAYA

Mouse                         KSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQNVQQVSYA

Rat                           KSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQNVQQVAYA

Pig                           KSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQNVQQVMYA

Bovine                        KSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQNVQQVVYA

Horse                         KSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQNVQQVAYA

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 – 1935	Myosin-7
Domain	85 – 778	Myosin motor

Literature citations

Skeletal muscle expression and abnormal function of beta-myosin in hypertrophic cardiomyopathy.
Cuda G.; Fananapazir L.; Zhu W.S.; Sellers J.R.; Epstein N.D.;
J. Clin. Invest. 91:2861-2865(1993)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 370-434; TISSUE SPECIFICITY; VARIANT GLN-403;

A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation.
Geisterfer-Lowrance A.A.T.; Kass S.; Tanigawa G.; Vosberg H.-P.; McKenna W.; Seidman C.E.; Seidman J.G.;
Cell 62:999-1006(1990)
Cited for: VARIANT CMH1 GLN-403;

Differences in clinical expression of hypertrophic cardiomyopathy associated with two distinct mutations in the beta-myosin heavy chain gene. A 908Leu-->Val mutation and a 403Arg-->Gln mutation.
Epstein N.D.; Cohn G.M.; Cyran F.; Fananapazir L.;
Circulation 86:345-352(1992)
Cited for: VARIANTS CMH1 GLN-403 AND VAL-908;

Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy.
Watkins H.; Rosenzweig A.; Hwang D.S.; Levi T.; McKenna W.; Seidmann C.E.; Seidmann J.G.;
N. Engl. J. Med. 326:1108-1114(1992)
Cited for: VARIANTS CMH1 GLN-249; GLN-403; CYS-453 AND MET-606;

Independent origin of identical beta cardiac myosin heavy-chain mutations in hypertrophic cardiomyopathy.
Watkins H.; Thierfelder L.; Anan R.; Jarcho J.; Matsumori A.; McKenna W.; Seidman J.G.; Seidman C.E.;
Am. J. Hum. Genet. 53:1180-1185(1993)
Cited for: VARIANTS CMH1 GLN-403; CYS-453; ARG-584 AND MET-606;

Low-density DNA microarrays are versatile tools to screen for known mutations in hypertrophic cardiomyopathy.
Waldmueller S.; Freund P.; Mauch S.; Toder R.; Vosberg H.-P.;
Hum. Mutat. 19:560-569(2002)
Cited for: VARIANTS CMH1 GLN-249; THR-349; GLN-403; ARG-595; MET-606; GLN-719; TRP-719; GLU-927 DEL AND LYS-1555;

Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy.
Richard P.; Charron P.; Carrier L.; Ledeuil C.; Cheav T.; Pichereau C.; Benaiche A.; Isnard R.; Dubourg O.; Burban M.; Gueffet J.-P.; Millaire A.; Desnos M.; Schwartz K.; Hainque B.; Komajda M.;
Circulation 107:2227-2232(2003)
Cited for: VARIANTS CMH1 MET-39; ASN-188; HIS-204; SER-232; GLN-249; THR-263; THR-355; LEU-403; GLN-403; TRP-403; VAL-428; THR-443; CYS-453; SER-479; LYS-483; MET-606; ILE-659; SER-663; HIS-663; CYS-671; ARG-716; GLN-719; TRP-719; CYS-723; GLU-733; ARG-741; ARG-768; GLU-778; HIS-787; THR-852; GLY-869; GLU-883 DEL; GLU-930 DEL; ARG-1135; GLN-1218; MET-1377; THR-1379; TRP-1382; MET-1692 AND THR-1777;

Utility of genetic screening in hypertrophic cardiomyopathy: prevalence and significance of novel and double (homozygous and heterozygous) beta-myosin mutations.
Mohiddin S.A.; Begley D.A.; McLam E.; Cardoso J.-P.; Winkler J.B.; Sellers J.R.; Fananapazir L.;
Genet. Test. 7:21-27(2003)
Cited for: VARIANTS CMH1 GLY-143; ILE-148; GLN-207; LEU-211; GLU-351; GLN-403; SER-479; ALA-500; ARG-571; HIS-663; CYS-671; THR-736; GLY-763; ASN-782; LEU-822; GLU-882 AND VAL-908;

Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis.
Woo A.; Rakowski H.; Liew J.C.; Zhao M.-S.; Liew C.-C.; Parker T.G.; Zeller M.; Wigle E.D.; Sole M.J.;
Heart 89:1179-1185(2003)
Cited for: VARIANTS CMH1 THR-196; LEU-211; GLN-249; GLN-403; LEU-404; ILE-411; CYS-453; ARG-716; CYS-870; VAL-908 AND LYS-930;

Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy.
Van Driest S.L.; Jaeger M.A.; Ommen S.R.; Will M.L.; Gersh B.J.; Tajik A.J.; Ackerman M.J.;
J. Am. Coll. Cardiol. 44:602-610(2004)
Cited for: VARIANTS CMH1 HIS-115; GLN-143; MET-263; CYS-312; THR-349; VAL-385; GLN-403; MET-404; VAL-407; VAL-428; MET-440; CYS-453; THR-511; ARG-515; CYS-663; HIS-663; CYS-694; ARG-716; GLN-719; ARG-741; VAL-778; THR-797; LYS-847 DEL; CYS-858; HIS-869; GLY-894; VAL-908; LYS-921; LYS-924; LYS-931; HIS-953; SER-1057; LYS-1356; MET-1377; TRP-1420; ASN-1459; SER-1513; LYS-1768; MET-1854 AND MET-1929; VARIANTS CYS-1491 AND ASN-1919;

Denaturing high performance liquid chromatography: high throughput mutation screening in familial hypertrophic cardiomyopathy and SNP genotyping in motor neurone disease.
Yu B.; Sawyer N.A.; Caramins M.; Yuan Z.G.; Saunderson R.B.; Pamphlett R.; Richmond D.R.; Jeremy R.W.; Trent R.J.;
J. Clin. Pathol. 58:479-485(2005)
Cited for: VARIANTS CMH1 VAL-227; GLY-328; GLU-351; GLN-403; TRP-403; ILE-411; THR-435; CYS-453; HIS-453; MET-606; CYS-663; GLN-719; TRP-719; HIS-787; GLY-894; VAL-908 AND LYS-927; VARIANT CYS-1519;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P12883: Variant p.Arg403Gln