TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23157	69694;69695;69696	chr2:178576775;178576774;178576773	chr2:179441502;179441501;179441500
N2AB	21516	64771;64772;64773	chr2:178576775;178576774;178576773	chr2:179441502;179441501;179441500
N2A	20589	61990;61991;61992	chr2:178576775;178576774;178576773	chr2:179441502;179441501;179441500
N2B	14092	42499;42500;42501	chr2:178576775;178576774;178576773	chr2:179441502;179441501;179441500
Novex-1	14217	42874;42875;42876	chr2:178576775;178576774;178576773	chr2:179441502;179441501;179441500
Novex-2	14284	43075;43076;43077	chr2:178576775;178576774;178576773	chr2:179441502;179441501;179441500
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-56
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1761
• 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
T/A	rs1362003473	-0.75	0.958	N	0.462	0.279	0.349429436713	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94175E-04	None	0	0	0	0	0
T/A	rs1362003473	-0.75	0.958	N	0.462	0.279	0.349429436713	gnomAD-4.0.0	6.57514E-06	None	None	None	None	N	None	0	0	None	0	1.94175E-04	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
T/A	0.1727	likely_benign	0.2086	benign	-0.892	Destabilizing	0.958	D	0.462	neutral	N	0.474802279	None	None	N
T/C	0.6767	likely_pathogenic	0.6828	pathogenic	-0.772	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
T/D	0.8764	likely_pathogenic	0.8882	pathogenic	-0.994	Destabilizing	0.998	D	0.758	deleterious	None	None	None	None	N
T/E	0.8199	likely_pathogenic	0.8317	pathogenic	-0.965	Destabilizing	0.995	D	0.728	prob.delet.	None	None	None	None	N
T/F	0.4552	ambiguous	0.434	ambiguous	-1.052	Destabilizing	0.991	D	0.802	deleterious	None	None	None	None	N
T/G	0.63	likely_pathogenic	0.6892	pathogenic	-1.161	Destabilizing	0.995	D	0.71	prob.delet.	None	None	None	None	N
T/H	0.6597	likely_pathogenic	0.6766	pathogenic	-1.539	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
T/I	0.2677	likely_benign	0.244	benign	-0.258	Destabilizing	0.976	D	0.667	neutral	N	0.481309966	None	None	N
T/K	0.7882	likely_pathogenic	0.7938	pathogenic	-0.804	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	N
T/L	0.181	likely_benign	0.1696	benign	-0.258	Destabilizing	0.086	N	0.373	neutral	None	None	None	None	N
T/M	0.1188	likely_benign	0.1157	benign	0.114	Stabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
T/N	0.4185	ambiguous	0.4643	ambiguous	-0.966	Destabilizing	0.998	D	0.677	prob.neutral	N	0.480322461	None	None	N
T/P	0.8479	likely_pathogenic	0.87	pathogenic	-0.438	Destabilizing	0.998	D	0.775	deleterious	N	0.519190771	None	None	N
T/Q	0.6667	likely_pathogenic	0.6843	pathogenic	-1.165	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
T/R	0.7045	likely_pathogenic	0.7111	pathogenic	-0.597	Destabilizing	0.995	D	0.777	deleterious	None	None	None	None	N
T/S	0.2382	likely_benign	0.2875	benign	-1.163	Destabilizing	0.979	D	0.46	neutral	N	0.514017131	None	None	N
T/V	0.1614	likely_benign	0.1435	benign	-0.438	Destabilizing	0.938	D	0.441	neutral	None	None	None	None	N
T/W	0.793	likely_pathogenic	0.7907	pathogenic	-1.017	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
T/Y	0.5706	likely_pathogenic	0.5753	pathogenic	-0.726	Destabilizing	0.995	D	0.821	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.