TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20166	60721;60722;60723	chr2:178591229;178591228;178591227	chr2:179455956;179455955;179455954
N2AB	18525	55798;55799;55800	chr2:178591229;178591228;178591227	chr2:179455956;179455955;179455954
N2A	17598	53017;53018;53019	chr2:178591229;178591228;178591227	chr2:179455956;179455955;179455954
N2B	11101	33526;33527;33528	chr2:178591229;178591228;178591227	chr2:179455956;179455955;179455954
Novex-1	11226	33901;33902;33903	chr2:178591229;178591228;178591227	chr2:179455956;179455955;179455954
Novex-2	11293	34102;34103;34104	chr2:178591229;178591228;178591227	chr2:179455956;179455955;179455954
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-120
• Domain position: 87
• Structural Position: 174
• Q(SASA): 0.0838
• 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/H	None	None	1.0	N	0.867	0.677	0.882114022096	gnomAD-4.0.0	1.3687E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79923E-06	0	0
L/I	None	None	0.248	N	0.331	0.236	0.580087410829	gnomAD-4.0.0	1.59203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43336E-05	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	0.8974	likely_pathogenic	0.8986	pathogenic	-2.966	Highly Destabilizing	0.97	D	0.739	prob.delet.	None	None	None	None	N
L/C	0.8232	likely_pathogenic	0.8291	pathogenic	-2.378	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.9994	pathogenic	-3.637	Highly Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
L/E	0.9953	likely_pathogenic	0.9961	pathogenic	-3.327	Highly Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
L/F	0.5864	likely_pathogenic	0.6709	pathogenic	-1.814	Destabilizing	0.994	D	0.748	deleterious	N	0.479977883	None	None	N
L/G	0.9859	likely_pathogenic	0.9878	pathogenic	-3.593	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
L/H	0.9839	likely_pathogenic	0.9872	pathogenic	-3.179	Highly Destabilizing	1.0	D	0.867	deleterious	N	0.510705891	None	None	N
L/I	0.127	likely_benign	0.1421	benign	-1.092	Destabilizing	0.248	N	0.331	neutral	N	0.510233039	None	None	N
L/K	0.9916	likely_pathogenic	0.9924	pathogenic	-2.433	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
L/M	0.2515	likely_benign	0.2691	benign	-1.187	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	N
L/N	0.994	likely_pathogenic	0.9941	pathogenic	-3.061	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
L/P	0.9955	likely_pathogenic	0.997	pathogenic	-1.706	Destabilizing	0.998	D	0.872	deleterious	N	0.510705891	None	None	N
L/Q	0.9783	likely_pathogenic	0.98	pathogenic	-2.766	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
L/R	0.9835	likely_pathogenic	0.9858	pathogenic	-2.324	Highly Destabilizing	0.998	D	0.838	deleterious	N	0.510705891	None	None	N
L/S	0.9858	likely_pathogenic	0.9868	pathogenic	-3.724	Highly Destabilizing	0.996	D	0.838	deleterious	None	None	None	None	N
L/T	0.9172	likely_pathogenic	0.9168	pathogenic	-3.243	Highly Destabilizing	0.97	D	0.781	deleterious	None	None	None	None	N
L/V	0.1148	likely_benign	0.126	benign	-1.706	Destabilizing	0.122	N	0.329	neutral	N	0.388786695	None	None	N
L/W	0.9691	likely_pathogenic	0.9802	pathogenic	-2.259	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
L/Y	0.963	likely_pathogenic	0.972	pathogenic	-2.023	Highly Destabilizing	0.999	D	0.805	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.