TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25046	75361;75362;75363	chr2:178570996;178570995;178570994	chr2:179435723;179435722;179435721
N2AB	23405	70438;70439;70440	chr2:178570996;178570995;178570994	chr2:179435723;179435722;179435721
N2A	22478	67657;67658;67659	chr2:178570996;178570995;178570994	chr2:179435723;179435722;179435721
N2B	15981	48166;48167;48168	chr2:178570996;178570995;178570994	chr2:179435723;179435722;179435721
Novex-1	16106	48541;48542;48543	chr2:178570996;178570995;178570994	chr2:179435723;179435722;179435721
Novex-2	16173	48742;48743;48744	chr2:178570996;178570995;178570994	chr2:179435723;179435722;179435721
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: Fn3-70
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0805
• Predicted PPI site: N

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/E	None	None	0.805	N	0.457	0.228	0.260735089382	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-06	0	0
K/R	None	None	0.025	N	0.381	0.1	0.27855597813	gnomAD-4.0.0	1.36871E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79931E-06	0	0
K/T	rs759445513	-1.796	0.967	N	0.659	0.396	0.363356657567	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	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	0.9039	likely_pathogenic	0.8853	pathogenic	-1.453	Destabilizing	0.916	D	0.507	neutral	None	None	None	None	N
K/C	0.8445	likely_pathogenic	0.8394	pathogenic	-1.436	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
K/D	0.9874	likely_pathogenic	0.9855	pathogenic	-1.596	Destabilizing	0.975	D	0.657	neutral	None	None	None	None	N
K/E	0.7687	likely_pathogenic	0.7428	pathogenic	-1.323	Destabilizing	0.805	D	0.457	neutral	N	0.515363926	None	None	N
K/F	0.9801	likely_pathogenic	0.979	pathogenic	-0.707	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
K/G	0.9413	likely_pathogenic	0.9322	pathogenic	-1.901	Destabilizing	0.916	D	0.649	neutral	None	None	None	None	N
K/H	0.7352	likely_pathogenic	0.7208	pathogenic	-1.927	Destabilizing	0.997	D	0.703	prob.neutral	None	None	None	None	N
K/I	0.8959	likely_pathogenic	0.8955	pathogenic	-0.19	Destabilizing	0.983	D	0.825	deleterious	N	0.495869049	None	None	N
K/L	0.7422	likely_pathogenic	0.7331	pathogenic	-0.19	Destabilizing	0.916	D	0.649	neutral	None	None	None	None	N
K/M	0.5654	likely_pathogenic	0.5333	ambiguous	-0.618	Destabilizing	0.997	D	0.7	prob.neutral	None	None	None	None	N
K/N	0.9374	likely_pathogenic	0.9315	pathogenic	-1.554	Destabilizing	0.967	D	0.557	neutral	N	0.480727308	None	None	N
K/P	0.9982	likely_pathogenic	0.9981	pathogenic	-0.591	Destabilizing	0.987	D	0.717	prob.delet.	None	None	None	None	N
K/Q	0.3571	ambiguous	0.3367	benign	-1.269	Destabilizing	0.204	N	0.302	neutral	N	0.482616789	None	None	N
K/R	0.0808	likely_benign	0.0816	benign	-0.985	Destabilizing	0.025	N	0.381	neutral	N	0.402366494	None	None	N
K/S	0.9561	likely_pathogenic	0.9479	pathogenic	-2.103	Highly Destabilizing	0.916	D	0.497	neutral	None	None	None	None	N
K/T	0.8492	likely_pathogenic	0.8274	pathogenic	-1.592	Destabilizing	0.967	D	0.659	neutral	N	0.489032194	None	None	N
K/V	0.854	likely_pathogenic	0.8496	pathogenic	-0.591	Destabilizing	0.975	D	0.707	prob.neutral	None	None	None	None	N
K/W	0.9608	likely_pathogenic	0.9613	pathogenic	-0.741	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
K/Y	0.9267	likely_pathogenic	0.9233	pathogenic	-0.391	Destabilizing	0.996	D	0.793	deleterious	None	None	None	None	N

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.