UniProtKB/Swiss-Prot Q8WZ42: Variant p.Thr4215Pro

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 4215 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 Threonine (T) to Proline (P) at position 4215 (T4215P, p.Thr4215Pro). 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 polar (T) to medium size and hydrophobic (P) 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
Other resources: Links to websites of interest for the variant.

• Variant rs2562829 [ dbSNP | Ensembl ]

Sequence information

Variant position: 4215 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 34350 The length of the canonical sequence.
Location on the sequence: GSQKVEPITEPEVESKYLIS T EEVSYFNVQSRVKYLDATPV 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 – 34350	Titin
Alternative sequence	3454 – 4380	Missing. In isoform 4 and isoform 11.
Alternative sequence	3455 – 5604	FSSSFLSAEEEGLHSAELQLSKINETLELLSESPVYPTKFDSEKEGTGPIFIKEVSNADISMGDVATLSVTVIGIPKPKIQWFFNGVLLTPSADYKFVFDGDDHSLIILFTKLEDEGEYTCMASNDYGKTICSAYLKINSKGEGHKDTETESAVAKSLEKLGGPCPPHFLKELKPIRCAQGLPAIFEYTVVGEPAPTVTWFKENKQLCTSVYYTIIHNPNGSGTFIVNDPQREDSGLYICKAENMLGESTCAAELLVLLEDTDMTDTPCKAKSTPEAPEDFPQTPLKGPAVEALDSEQEIATFVKDTILKAALITEENQQLSYEHIAKANELSSQLPLGAQELQSILEQDKLTPESTREFLCINGSIHFQPLKEPSPNLQLQIVQSQKTFSKEGILMPEEPETQAVLSDTEKIFPSAMSIEQINSLTVEPLKTLLAEPEGNYPQSSIEPPMHSYLTSVAEEVLSPKEKTVSDTNREQRVTLQKQEAQSALILSQSLAEGHVESLQSPDVMISQVNYEPLVPSEHSCTEGGKILIESANPLENAGQDSAVRIEEGKSLRFPLALEEKQVLLKEEHSDNVVMPPDQIIESKREPVAIKKVQEVQGRDLLSKESLLSGIPEEQRLNLKIQICRALQAAVASEQPGLFSEWLRNIEKVEVEAVNITQEPRHIMCMYLVTSAKSVTEEVTIIIEDVDPQMANLKMELRDALCAIIYEEIDILTAEGPRIQQGAKTSLQEEMDSFSGSQKVEPITEPEVESKYLISTEEVSYFNVQSRVKYLDATPVTKGVASAVVSDEKQDESLKPSEEKEESSSESGTEEVATVKIQEAEGGLIKEDGPMIHTPLVDTVSEEGDIVHLTTSITNAKEVNWYFENKLVPSDEKFKCLQDQNTYTLVIDKVNTEDHQGEYVCEALNDSGKTATSAKLTVVKRAAPVIKRKIEPLEVALGHLAKFTCEIQSAPNVRFQWFKAGREIYESDKCSIRSSKYISSLEILRTQVVDCGEYTCKASNEYGSVSCTATLTVTEAYPPTFLSRPKSLTTFVGKAAKFICTVTGTPVIETIWQKDGAALSPSPNWRISDAENKHILELSNLTIQDRGVYSCKASNKFGADICQAELIIIDKPHFIKELEPVQSAINKKVHLECQVDEDRKVTVTWSKDGQKLPPGKDYKICFEDKIATLEIPLAKLKDSGTYVCTASNEAGSSSCSATVTVREPPSFVKKVDPSYLMLPGESARLHCKLKGSPVIQVTWFKNNKELSESNTVRMYFVNSEAILDITDVKVEDSGSYSCEAVNDVGSDSCSTEIVIKEPPSFIKTLEPADIVRGTNALLQCEVSGTGPFEISWFKDKKQIRSSKKYRLFSQKSLVCLEIFSFNSADVGEYECVVANEVGKCGCMATHLLKEPPTFVKKVDDLIALGGQTVTLQAAVRGSEPISVTWMKGQEVIREDGKIKMSFSNGVAVLIIPDVQISFGGKYTCLAENEAGSQTSVGELIVKEPAKIIERAELIQVTAGDPATLEYTVAGTPELKPKWYKDGRPLVASKKYRISFKNNVAQLKFYSAELHDSGQYTFEISNEVGSSSCETTFTVLDRDIAPFFTKPLRNVDSVVNGTCRLDCKIAGSLPMRVSWFKDGKEIAASDRYRIAFVEGTASLEIIRVDMNDAGNFTCRATNSVGSKDSSGALIVQEPPSFVTKPGSKDVLPGSAVCLKSTFQGSTPLTIRWFKGNKELVSGGSCYITKEALESSLELYLVKTSDSGTYTCKVSNVAGGVECSANLFVKEPATFVEKLEPSQLLKKGDATQLACKVTGTPPIKITWFANDREIKESSKHRMSFVESTAVLRLTDVGIEDSGEYMCEAQNEAGSDHCSSIVIVKESPYFTKEFKPIEVLKEYDVMLLAEVAGTPPFEITWFKDNTILRSGRKYKTFIQDHLVSLQILKFVAADAGEYQCRVTNEVGSSICSARVTLREPPSFIKKIESTSSLRGGTAAFQATLKGSLPITVTWLKDSDEITEDDNIRMTFENNVASLYLSGIEVKHDGKYVCQAKNDAGIQRCSALLSVKEPATITEEAVSIDVTQGDPATLQVKFSGTKEITAKWFKDGQELTLGSKYKISVTDTVSILKIISTEKKDSGEYTFEVQNDVGRSSCKARINVLDLIIPPSF -> LFSEGESEHSERDTRDAFSDSEDIDHKSMAAKRYASRISSTSSWPEYFKPSFTQKLTFKYVLEGEPVVFTCRLIACPTPEMTWFHNNRPIPTGLRRIIKAESDLHHHSSSLEIKRVQDRDSGSYRLLAINSEGSAESTASLLVIQKGQDEKYLEFLKRAERTHENVEALVERGEDRIKVDLRFTGSPFNKKQDVEQKGMMRTIHFKTMSSAKKTDYMYDEEYLESKSDIRGWLNVGESFLDKETKVKLQRLREARKTLMEKKKLSLLDTSSEISSRTLRSEASDKDILFSREDMKIRSMSDLAESYKVDHSAESIVQNPHALSNQMDQNIESEELPTSFQTIVDEEIFQTEIRMSQEALVKESLPKDHLYGEILVNENTQARGQLEEIMANTTIGESSTYITNVCEKEEVYETPENVSQAITPHASESFGTLVNVEESEEIASERIKKDDLRELQLSASTRIDEFKTEQKEENMRFFENSFRKRPQRCPPSFLQEIESQEVYEGDSCNFVCHFQGYPQPIVTWYNNDMPIPRNQNFIIHSLENYSILTLSSVHHQNEGSITCVLFNQYGTVKTTSMLKVKAKQKHDVKAHKVPVFHDYLDEEEELALVFDQAKGAHPSMSQEGQTNLHLLKTNPPVPPSGDTELLSFPVEIQVTAATPIPEQDKESKEVFQTEELEPKAMPQDQVTQSPKHRFVFLSDITNEPPKMLQEMPKHARCREGDSIILECLISGEPQPVVTWFQNGVLLKQNQKFQFEEVNCSHQLYIKDVNSQDSGKYKCVAENNSGAVESVSDLTVEPVTYRENSQFENIGEIYGKYSRDQQLQDQGESVRAHFYDYPAGPFTPWTNVKEYSVRDYFQSLETIEQIDQKEQVRCIPSREKIPRFVHGASRTIKISKPIRAEFIQCQAEGKERHVSEKSKLHQAEGTVYPFVDDFSDVTIKKEIRNNFGKLGRSEKENVQECAQSDYLPNIHSERISDSYNTKDSSAIVYEESLGEEIHYPGKKVKHRIIEFEKLHVEKGVLEKRPTRTSIVNPPQKKIDDKAFSLKQRESRSSNLNANMYQAEKMSPNTESDSSNIAINLKLLSSQTHKEFDAQEREQQEKISLIDKPAISKRAEHESPITFDLKQFHTQIKHTDVKFQELDSGQPEEAYFKIQHPADTENIVFDLKQMYSHIGDPALEFQGQETREQQEIHYKEKIPSPETLQPDTHNISKSVQNNVFASQEISSSQELSNRTMVEKSSIDENSISLEKEVRHVQEQNLDILKTDLSLKSFSEEIYSESCALLPTSSADIEETDLSEKSCPLENGGRSSISHLKKAASEEKPLGVGEMEEECTLEPELAAFPKQDGGTQEYTDATLEDHRGDVQEADTLHRQLSLSQCFPLLMTEEQQNPGEQISTNIHASGEEKCYEEVQVQNEASFSTLEGEMIETSFSQNIPKLDEAHTTEAAESETSLTQYLLAAGKREVPETKDTRDQAKLVQSESITSMEVEEVTFNTVYEYYNQKQESLGRPLSPESDISIGVGSTTSEEISELDQFYTPPSSVEYFESPKSPDLYFNPSDITKQSSIHSGGETVERYSTPLGEVAERYSTPSEGEVGERYSTPPGETLERYSTPPGETLERYSTPPGETLERYSTPPGETLERYSTPPGETLERYSTPPGEALERYSIPTGGPNPTGTFKTYPSKIEREDGTPNEHFYTPTEERGSAYEIWRSDSFGTPNEAIEPKDNEMPPSFIEPLTKRKVYENTTLGFIVEVEGLPVPGVKWYRNKSLLEPDERIKMERVGNVCSLEISNIQKGEGGEYMCHAVNIIGEAKSFANVDIMPQEERVVALPPPVTHQHVMEFDLEHTTSSRTPSPQEIVLEVELSEKDVKEFEKQVKIVTVPEFTPDHKSMIVSLDVLPFNFVDPNMDSREGEDKELKIDLEVFEMPPRFIMPICDFKIPENSDAVFKCSVIGIPTPEVKWYKEYMCIEPDNIKYVISEEKGSHTLKIRNVCLSDSATYRCRAVNCVGEAICRGFLTMGDSEIFAVIAKKSKVTLSSLMEELVLKSNYTDSFFEFQVVEGPPRFIKGISDCYAPIGTAAYFQCLVRGSPRPTVYWYKDGKLVQGRRFTVEESGTGFHNLFITSLVKSDEGEYRCVATNKSGMAESFAALTLT. In isoform 6.
Alternative sequence	3646 – 4380	Missing. In isoform 7.

Literature citations

Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity.
Freiburg A.; Trombitas K.; Hell W.; Cazorla O.; Fougerousse F.; Centner T.; Kolmerer B.; Witt C.; Beckmann J.S.; Gregorio C.C.; Granzier H.; Labeit S.;
Circ. Res. 86:1114-1121(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; ALTERNATIVE SPLICING; VARIANTS LEU-1295; GLN-1572; ILE-2610; ASN-2831; SER-3491; PRO-4215; PHE-4283 AND ARG-12383; The complete gene sequence of titin, expression of an unusual ~700 kDa titin isoform and its interaction with obscurin identify a novel Z-line to I-band linking system.
Bang M.-L.; Centner T.; Fornoff F.; Geach A.J.; Gotthardt M.; McNabb M.; Witt C.C.; Labeit D.; Gregorio C.C.; Granzier H.; Labeit S.;
Circ. Res. 89:1065-1072(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; ALTERNATIVE SPLICING; TISSUE SPECIFICITY; INTERACTION WITH OBSCN; VARIANTS LEU-1295; GLN-1572; ILE-2610; ASN-2831; SER-3491; PRO-4215 AND PHE-4283; Familial dilated cardiomyopathy locus maps to chromosome 2q31.
Siu B.L.; Niimura H.; Osborne J.A.; Fatkin D.; MacRae C.; Solomon S.; Benson D.W.; Seidman J.G.; Seidman C.E.;
Circulation 99:1022-1026(1999)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3455-4473; VARIANTS PRO-4215 AND PHE-4283; Titin mutations as the molecular basis for dilated cardiomyopathy.
Itoh-Satoh M.; Hayashi T.; Nishi H.; Koga Y.; Arimura T.; Koyanagi T.; Takahashi M.; Hohda S.; Ueda K.; Nouchi T.; Hiroe M.; Marumo F.; Imaizumi T.; Yasunami M.; Kimura A.;
Biochem. Biophys. Res. Commun. 291:385-393(2002)
Cited for: VARIANTS CMD1G MET-54; VAL-743; TYR-3799 AND ASN-4465; VARIANTS CYS-328; GLN-4084 AND PRO-4215; CHARACTERIZATION OF VARIANTS CMD1G MET-54 AND VAL-743; FUNCTION; Patterns of somatic mutation in human cancer genomes.
Greenman C.; Stephens P.; Smith R.; Dalgliesh G.L.; Hunter C.; Bignell G.; Davies H.; Teague J.; Butler A.; Stevens C.; Edkins S.; O'Meara S.; Vastrik I.; Schmidt E.E.; Avis T.; Barthorpe S.; Bhamra G.; Buck G.; Choudhury B.; Clements J.; Cole J.; Dicks E.; Forbes S.; Gray K.; Halliday K.; Harrison R.; Hills K.; Hinton J.; Jenkinson A.; Jones D.; Menzies A.; Mironenko T.; Perry J.; Raine K.; Richardson D.; Shepherd R.; Small A.; Tofts C.; Varian J.; Webb T.; West S.; Widaa S.; Yates A.; Cahill D.P.; Louis D.N.; Goldstraw P.; Nicholson A.G.; Brasseur F.; Looijenga L.; Weber B.L.; Chiew Y.-E.; DeFazio A.; Greaves M.F.; Green A.R.; Campbell P.; Birney E.; Easton D.F.; Chenevix-Trench G.; Tan M.-H.; Khoo S.K.; Teh B.T.; Yuen S.T.; Leung S.Y.; Wooster R.; Futreal P.A.; Stratton M.R.;
Nature 446:153-158(2007)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] TYR-60; MET-115; CYS-328; THR-360; ILE-498; MET-799; ILE-811; HIS-922; ASP-937; THR-1081; ARG-1137; GLU-1201; ALA-1202; LEU-1295; ASP-1345; THR-1347; HIS-1350; LEU-1353; VAL-1393; CYS-1416; PRO-1441; VAL-1544; GLN-1572; GLY-1658; GLN-1664; ASP-1692; LEU-1744; GLY-1772; ILE-1907; HIS-1998; LEU-2107; THR-2118; THR-2164; TYR-2240; SER-2392; PHE-2432; ILE-2610; MET-2771; PHE-2823; ASN-2831; ILE-2930; ARG-3154; GLU-3191; LEU-3238; GLY-3250; MET-3261; GLN-3367; LYS-3482; LYS-3570; VAL-3590; VAL-3762; PHE-3877; LEU-3965; PRO-4215; TRP-4238; PHE-4283; THR-4291; ASP-4303; GLU-4427; GLU-12310; ALA-12469; CYS-12642; LYS-12657; GLU-12679; PHE-12720; CYS-12798; GLY-13049; LYS-13083; LEU-13096; ARG-13099; ALA-13297; MET-13399; THR-13418; VAL-13428; THR-13430; LYS-13434; ASN-13469; ASN-13495; SER-13785; HIS-13870; ILE-14109; GLN-14131; THR-14208; VAL-14728; THR-14999; THR-15021; VAL-15520; ILE-15555; GLN-15620; ILE-15629; CYS-15635; GLN-15700; PRO-15705; MET-15837; HIS-16058; ILE-16067; THR-16090; HIS-16195; CYS-16409; PRO-16424; MET-16629; ARG-16877; ASP-17060; VAL-17637; HIS-17838; ASN-17866; GLU-17906; ALA-18094; SER-18109; THR-18164; LEU-18221; THR-18222; GLN-18726; ALA-18835; LYS-18881; SER-18939; GLN-19000; GLN-19060; LYS-19091; SER-19224; ILE-19367; LYS-19392; SER-19480; GLY-19495; HIS-19665; ILE-19762; ARG-19947; MET-19956; GLN-19992; CYS-20057; LEU-20075; LYS-20179; THR-20198; VAL-20198; HIS-20331; THR-20408; LYS-20564; ILE-20718; PRO-20726; ASN-20892; ARG-20894; GLU-21125; SER-21403; CYS-21730; GLN-21747; ARG-21851; ARG-21851; ARG-21925; HIS-21995; VAL-22045; HIS-22149; ILE-22160; THR-22261; ASN-22306; HIS-22357; PRO-22408; HIS-22537; LEU-22584; PRO-22646; ALA-22670; ASP-22770; THR-22801; TRP-22823; GLN-22968; LEU-23074; PHE-23079; ASN-23282; TYR-23303; CYS-23306; SER-23515; GLN-23551; ASN-23807; ASN-23872; ALA-23891; HIS-23933; MET-23939; LEU-23952; GLY-24098; SER-24119; ILE-24133; ALA-24159; ALA-24239; LYS-24265; THR-24584; THR-24781; HIS-24799; HIS-24954; MET-24980; HIS-25659; THR-25679; ALA-25720; LYS-25821; LYS-25859; LYS-25879; VAL-25923; ILE-26045; GLU-26059; VAL-26134; CYS-26477; TYR-26843; ARG-27346; CYS-27652; VAL-27728; LEU-27754; THR-27755; VAL-27929; LEU-28132; GLN-28168; HIS-28538; THR-28572; THR-28948; VAL-28986; GLU-28993; VAL-28998; MET-29070; VAL-29090; CYS-29419; PRO-29479; LEU-29880; GLU-29976; GLY-30042; CYS-30107; PHE-30125; PRO-30211; THR-30412; SER-30617; ILE-30674; ILE-30809; ILE-30818; LYS-30825; THR-30856; ASP-30887; SER-30887; HIS-30897; HIS-30907; HIS-30946; PHE-31081; CYS-31107; GLY-31124; SER-31156; THR-31246; HIS-31330; ARG-31690; GLN-31724; ILE-31725; SER-31732; ILE-31886; CYS-32097; ASN-32171; ILE-32248; HIS-32281; HIS-32323; TRP-32411; VAL-32558; VAL-32610; VAL-32637; ALA-32922; ARG-32943; HIS-32953; LEU-33213; CYS-33242; MET-33387; ASP-33419; MET-33536; GLN-33568; LYS-33616; LEU-33620; VAL-33886; THR-33899; PRO-33904; ILE-33955 AND ALA-34115;