TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27295	82108;82109;82110	chr2:178564249;178564248;178564247	chr2:179428976;179428975;179428974
N2AB	25654	77185;77186;77187	chr2:178564249;178564248;178564247	chr2:179428976;179428975;179428974
N2A	24727	74404;74405;74406	chr2:178564249;178564248;178564247	chr2:179428976;179428975;179428974
N2B	18230	54913;54914;54915	chr2:178564249;178564248;178564247	chr2:179428976;179428975;179428974
Novex-1	18355	55288;55289;55290	chr2:178564249;178564248;178564247	chr2:179428976;179428975;179428974
Novex-2	18422	55489;55490;55491	chr2:178564249;178564248;178564247	chr2:179428976;179428975;179428974
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-140
• Domain position: 18
• Structural Position: 30
• Q(SASA): 0.1169
• 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
L/V	None	None	0.9	D	0.474	0.484	0.660250038783	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.836	likely_pathogenic	0.8458	pathogenic	-1.394	Destabilizing	0.983	D	0.725	prob.delet.	None	None	None	None	N
L/C	0.8637	likely_pathogenic	0.8655	pathogenic	-1.166	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.9992	pathogenic	-2.351	Highly Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
L/E	0.993	likely_pathogenic	0.9941	pathogenic	-2.111	Highly Destabilizing	0.999	D	0.866	deleterious	None	None	None	None	N
L/F	0.4204	ambiguous	0.3921	ambiguous	-1.03	Destabilizing	0.997	D	0.729	prob.delet.	D	0.535502417	None	None	N
L/G	0.9843	likely_pathogenic	0.986	pathogenic	-1.811	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
L/H	0.983	likely_pathogenic	0.985	pathogenic	-2.074	Highly Destabilizing	1.0	D	0.836	deleterious	D	0.623113421	None	None	N
L/I	0.1052	likely_benign	0.1063	benign	-0.147	Destabilizing	0.198	N	0.279	neutral	N	0.503820307	None	None	N
L/K	0.9897	likely_pathogenic	0.9916	pathogenic	-1.327	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
L/M	0.1885	likely_benign	0.1865	benign	-0.549	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
L/N	0.9951	likely_pathogenic	0.9962	pathogenic	-1.98	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
L/P	0.9896	likely_pathogenic	0.9896	pathogenic	-0.555	Destabilizing	0.999	D	0.863	deleterious	D	0.623113421	None	None	N
L/Q	0.9757	likely_pathogenic	0.9785	pathogenic	-1.562	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
L/R	0.9793	likely_pathogenic	0.9814	pathogenic	-1.793	Destabilizing	0.999	D	0.845	deleterious	D	0.623113421	None	None	N
L/S	0.9806	likely_pathogenic	0.9828	pathogenic	-2.23	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
L/T	0.9073	likely_pathogenic	0.9224	pathogenic	-1.854	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
L/V	0.1474	likely_benign	0.1532	benign	-0.555	Destabilizing	0.9	D	0.474	neutral	D	0.566617048	None	None	N
L/W	0.9113	likely_pathogenic	0.9035	pathogenic	-1.379	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
L/Y	0.9439	likely_pathogenic	0.9459	pathogenic	-1.146	Destabilizing	0.999	D	0.745	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.