TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18111	54556;54557;54558	chr2:178604758;178604757;178604756	chr2:179469485;179469484;179469483
N2AB	16470	49633;49634;49635	chr2:178604758;178604757;178604756	chr2:179469485;179469484;179469483
N2A	15543	46852;46853;46854	chr2:178604758;178604757;178604756	chr2:179469485;179469484;179469483
N2B	9046	27361;27362;27363	chr2:178604758;178604757;178604756	chr2:179469485;179469484;179469483
Novex-1	9171	27736;27737;27738	chr2:178604758;178604757;178604756	chr2:179469485;179469484;179469483
Novex-2	9238	27937;27938;27939	chr2:178604758;178604757;178604756	chr2:179469485;179469484;179469483
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: Fn3-19
• Domain position: 47
• Structural Position: 62
• Q(SASA): 0.6732
• 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/T	rs2054379596	None	0.117	N	0.313	0.116	0.221019684889	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/T	rs2054379596	None	0.117	N	0.313	0.116	0.221019684889	gnomAD-4.0.0	6.57877E-06	None	None	None	None	N	None	2.41289E-05	0	None	0	0	None	0	0	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	0.4654	ambiguous	0.3388	benign	-0.064	Destabilizing	0.067	N	0.349	neutral	None	None	None	None	N
K/C	0.8329	likely_pathogenic	0.7472	pathogenic	-0.581	Destabilizing	0.935	D	0.386	neutral	None	None	None	None	N
K/D	0.5842	likely_pathogenic	0.5125	ambiguous	-0.457	Destabilizing	0.149	N	0.31	neutral	None	None	None	None	N
K/E	0.4061	ambiguous	0.3085	benign	-0.48	Destabilizing	0.062	N	0.363	neutral	N	0.457718345	None	None	N
K/F	0.8307	likely_pathogenic	0.752	pathogenic	-0.458	Destabilizing	0.555	D	0.342	neutral	None	None	None	None	N
K/G	0.4349	ambiguous	0.3484	ambiguous	-0.155	Destabilizing	None	N	0.233	neutral	None	None	None	None	N
K/H	0.3927	ambiguous	0.326	benign	-0.2	Destabilizing	0.555	D	0.299	neutral	None	None	None	None	N
K/I	0.5484	ambiguous	0.4334	ambiguous	0.094	Stabilizing	0.484	N	0.339	neutral	N	0.473952905	None	None	N
K/L	0.5104	ambiguous	0.3798	ambiguous	0.094	Stabilizing	0.149	N	0.335	neutral	None	None	None	None	N
K/M	0.4071	ambiguous	0.3017	benign	-0.281	Destabilizing	0.935	D	0.301	neutral	None	None	None	None	N
K/N	0.4447	ambiguous	0.366	ambiguous	-0.125	Destabilizing	0.117	N	0.308	neutral	N	0.462222874	None	None	N
K/P	0.667	likely_pathogenic	0.5492	ambiguous	0.062	Stabilizing	0.555	D	0.309	neutral	None	None	None	None	N
K/Q	0.2428	likely_benign	0.1912	benign	-0.259	Destabilizing	0.317	N	0.297	neutral	N	0.492583067	None	None	N
K/R	0.1001	likely_benign	0.0878	benign	-0.215	Destabilizing	None	N	0.25	neutral	N	0.452083238	None	None	N
K/S	0.5205	ambiguous	0.4087	ambiguous	-0.443	Destabilizing	0.149	N	0.337	neutral	None	None	None	None	N
K/T	0.2788	likely_benign	0.1998	benign	-0.369	Destabilizing	0.117	N	0.313	neutral	N	0.414815716	None	None	N
K/V	0.4786	ambiguous	0.3686	ambiguous	0.062	Stabilizing	0.38	N	0.331	neutral	None	None	None	None	N
K/W	0.816	likely_pathogenic	0.7506	pathogenic	-0.585	Destabilizing	0.935	D	0.445	neutral	None	None	None	None	N
K/Y	0.6789	likely_pathogenic	0.6058	pathogenic	-0.25	Destabilizing	0.555	D	0.335	neutral	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.