TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29909	89950;89951;89952	chr2:178553175;178553174;178553173	chr2:179417902;179417901;179417900
N2AB	28268	85027;85028;85029	chr2:178553175;178553174;178553173	chr2:179417902;179417901;179417900
N2A	27341	82246;82247;82248	chr2:178553175;178553174;178553173	chr2:179417902;179417901;179417900
N2B	20844	62755;62756;62757	chr2:178553175;178553174;178553173	chr2:179417902;179417901;179417900
Novex-1	20969	63130;63131;63132	chr2:178553175;178553174;178553173	chr2:179417902;179417901;179417900
Novex-2	21036	63331;63332;63333	chr2:178553175;178553174;178553173	chr2:179417902;179417901;179417900
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: Ig-147
• Domain position: 68
• Structural Position: 153
• Q(SASA): 0.6524
• 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	rs769543331	0.74	0.999	N	0.655	0.477	0.425499470309	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/E	rs769543331	0.74	0.999	N	0.655	0.477	0.425499470309	gnomAD-4.0.0	1.11393E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.00079E-05	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	0.7483	likely_pathogenic	0.6582	pathogenic	-0.294	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
K/C	0.8408	likely_pathogenic	0.7994	pathogenic	-0.411	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/D	0.8614	likely_pathogenic	0.7918	pathogenic	0.449	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/E	0.5276	ambiguous	0.4089	ambiguous	0.49	Stabilizing	0.999	D	0.655	neutral	N	0.518455451	None	None	N
K/F	0.9138	likely_pathogenic	0.8749	pathogenic	-0.392	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/G	0.8359	likely_pathogenic	0.785	pathogenic	-0.539	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/H	0.4562	ambiguous	0.3903	ambiguous	-0.833	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/I	0.5488	ambiguous	0.4519	ambiguous	0.285	Stabilizing	1.0	D	0.791	deleterious	D	0.531790108	None	None	N
K/L	0.62	likely_pathogenic	0.5417	ambiguous	0.285	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/M	0.4446	ambiguous	0.3641	ambiguous	0.16	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/N	0.6849	likely_pathogenic	0.5873	pathogenic	0.115	Stabilizing	1.0	D	0.727	prob.delet.	N	0.487164495	None	None	N
K/P	0.928	likely_pathogenic	0.8965	pathogenic	0.121	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
K/Q	0.284	likely_benign	0.2295	benign	-0.046	Destabilizing	1.0	D	0.712	prob.delet.	D	0.52722965	None	None	N
K/R	0.0992	likely_benign	0.097	benign	-0.102	Destabilizing	0.999	D	0.604	neutral	N	0.51976496	None	None	N
K/S	0.7504	likely_pathogenic	0.6608	pathogenic	-0.563	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
K/T	0.3875	ambiguous	0.3019	benign	-0.344	Destabilizing	1.0	D	0.769	deleterious	N	0.518783525	None	None	N
K/V	0.5553	ambiguous	0.4615	ambiguous	0.121	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/W	0.8778	likely_pathogenic	0.8335	pathogenic	-0.293	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/Y	0.7813	likely_pathogenic	0.7181	pathogenic	0.043	Stabilizing	1.0	D	0.761	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.