TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20943	63052;63053;63054	chr2:178588898;178588897;178588896	chr2:179453625;179453624;179453623
N2AB	19302	58129;58130;58131	chr2:178588898;178588897;178588896	chr2:179453625;179453624;179453623
N2A	18375	55348;55349;55350	chr2:178588898;178588897;178588896	chr2:179453625;179453624;179453623
N2B	11878	35857;35858;35859	chr2:178588898;178588897;178588896	chr2:179453625;179453624;179453623
Novex-1	12003	36232;36233;36234	chr2:178588898;178588897;178588896	chr2:179453625;179453624;179453623
Novex-2	12070	36433;36434;36435	chr2:178588898;178588897;178588896	chr2:179453625;179453624;179453623
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-39
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.5921
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/T	None	None	1.0	N	0.619	0.508	0.39798585902	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.7081	likely_pathogenic	0.7778	pathogenic	0.048	Stabilizing	0.999	D	0.591	neutral	None	None	None	None	I
K/C	0.9008	likely_pathogenic	0.9181	pathogenic	-0.306	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
K/D	0.8981	likely_pathogenic	0.9227	pathogenic	-0.169	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
K/E	0.6196	likely_pathogenic	0.6992	pathogenic	-0.172	Destabilizing	0.999	D	0.556	neutral	N	0.476786895	None	None	I
K/F	0.9554	likely_pathogenic	0.967	pathogenic	-0.231	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	I
K/G	0.807	likely_pathogenic	0.8713	pathogenic	-0.112	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	I
K/H	0.5778	likely_pathogenic	0.6064	pathogenic	-0.248	Destabilizing	1.0	D	0.578	neutral	None	None	None	None	I
K/I	0.7337	likely_pathogenic	0.771	pathogenic	0.388	Stabilizing	1.0	D	0.645	neutral	N	0.520367101	None	None	I
K/L	0.7114	likely_pathogenic	0.7503	pathogenic	0.388	Stabilizing	1.0	D	0.579	neutral	None	None	None	None	I
K/M	0.6123	likely_pathogenic	0.669	pathogenic	0.048	Stabilizing	1.0	D	0.576	neutral	None	None	None	None	I
K/N	0.8327	likely_pathogenic	0.8684	pathogenic	0.142	Stabilizing	1.0	D	0.657	neutral	N	0.4833702	None	None	I
K/P	0.8493	likely_pathogenic	0.8928	pathogenic	0.3	Stabilizing	1.0	D	0.61	neutral	None	None	None	None	I
K/Q	0.3259	likely_benign	0.3834	ambiguous	-0.008	Destabilizing	1.0	D	0.653	neutral	N	0.514843851	None	None	I
K/R	0.0962	likely_benign	0.1017	benign	-0.009	Destabilizing	0.999	D	0.479	neutral	N	0.499125037	None	None	I
K/S	0.8005	likely_pathogenic	0.8521	pathogenic	-0.258	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	I
K/T	0.55	ambiguous	0.6207	pathogenic	-0.129	Destabilizing	1.0	D	0.619	neutral	N	0.469936753	None	None	I
K/V	0.6666	likely_pathogenic	0.7193	pathogenic	0.3	Stabilizing	1.0	D	0.62	neutral	None	None	None	None	I
K/W	0.9261	likely_pathogenic	0.9474	pathogenic	-0.309	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
K/Y	0.8813	likely_pathogenic	0.9043	pathogenic	0.047	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.