TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24102	72529;72530;72531	chr2:178573828;178573827;178573826	chr2:179438555;179438554;179438553
N2AB	22461	67606;67607;67608	chr2:178573828;178573827;178573826	chr2:179438555;179438554;179438553
N2A	21534	64825;64826;64827	chr2:178573828;178573827;178573826	chr2:179438555;179438554;179438553
N2B	15037	45334;45335;45336	chr2:178573828;178573827;178573826	chr2:179438555;179438554;179438553
Novex-1	15162	45709;45710;45711	chr2:178573828;178573827;178573826	chr2:179438555;179438554;179438553
Novex-2	15229	45910;45911;45912	chr2:178573828;178573827;178573826	chr2:179438555;179438554;179438553
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-131
• Domain position: 74
• Structural Position: 156
• Q(SASA): 0.0707
• 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/R	None	None	0.997	N	0.891	0.602	0.766578170383	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
L/V	rs780348282	-1.198	0.117	N	0.416	0.132	0.380394304726	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
L/V	rs780348282	-1.198	0.117	N	0.416	0.132	0.380394304726	gnomAD-4.0.0	1.37012E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.32428E-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	0.9445	likely_pathogenic	0.9394	pathogenic	-3.012	Highly Destabilizing	0.966	D	0.761	deleterious	None	None	None	None	N
L/C	0.9063	likely_pathogenic	0.9047	pathogenic	-2.363	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.737	Highly Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
L/E	0.9983	likely_pathogenic	0.9972	pathogenic	-3.437	Highly Destabilizing	0.998	D	0.895	deleterious	None	None	None	None	N
L/F	0.7501	likely_pathogenic	0.7829	pathogenic	-1.773	Destabilizing	0.997	D	0.828	deleterious	N	0.484013812	None	None	N
L/G	0.9954	likely_pathogenic	0.9936	pathogenic	-3.614	Highly Destabilizing	0.998	D	0.895	deleterious	None	None	None	None	N
L/H	0.9956	likely_pathogenic	0.9934	pathogenic	-3.169	Highly Destabilizing	1.0	D	0.879	deleterious	N	0.508411944	None	None	N
L/I	0.1172	likely_benign	0.1345	benign	-1.204	Destabilizing	0.955	D	0.702	prob.neutral	N	0.468252264	None	None	N
L/K	0.9962	likely_pathogenic	0.9925	pathogenic	-2.362	Highly Destabilizing	0.998	D	0.884	deleterious	None	None	None	None	N
L/M	0.3707	ambiguous	0.3892	ambiguous	-1.335	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
L/N	0.9984	likely_pathogenic	0.9972	pathogenic	-2.985	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
L/P	0.998	likely_pathogenic	0.9965	pathogenic	-1.797	Destabilizing	0.999	D	0.899	deleterious	N	0.508411944	None	None	N
L/Q	0.9922	likely_pathogenic	0.9867	pathogenic	-2.71	Highly Destabilizing	0.999	D	0.89	deleterious	None	None	None	None	N
L/R	0.9915	likely_pathogenic	0.985	pathogenic	-2.224	Highly Destabilizing	0.997	D	0.891	deleterious	N	0.508411944	None	None	N
L/S	0.9965	likely_pathogenic	0.9953	pathogenic	-3.606	Highly Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
L/T	0.9806	likely_pathogenic	0.9757	pathogenic	-3.15	Highly Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	N
L/V	0.1329	likely_benign	0.1558	benign	-1.797	Destabilizing	0.117	N	0.416	neutral	N	0.482104209	None	None	N
L/W	0.9878	likely_pathogenic	0.9858	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/Y	0.9847	likely_pathogenic	0.9833	pathogenic	-2.032	Highly Destabilizing	0.999	D	0.847	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.