TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19635	59128;59129;59130	chr2:178593305;178593304;178593303	chr2:179458032;179458031;179458030
N2AB	17994	54205;54206;54207	chr2:178593305;178593304;178593303	chr2:179458032;179458031;179458030
N2A	17067	51424;51425;51426	chr2:178593305;178593304;178593303	chr2:179458032;179458031;179458030
N2B	10570	31933;31934;31935	chr2:178593305;178593304;178593303	chr2:179458032;179458031;179458030
Novex-1	10695	32308;32309;32310	chr2:178593305;178593304;178593303	chr2:179458032;179458031;179458030
Novex-2	10762	32509;32510;32511	chr2:178593305;178593304;178593303	chr2:179458032;179458031;179458030
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-30
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.3643
• 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
P/R	None	None	1.0	N	0.811	0.41	0.459192005304	gnomAD-4.0.0	1.59202E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-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
P/A	0.1945	likely_benign	0.1681	benign	-0.643	Destabilizing	1.0	D	0.743	deleterious	N	0.48486766	None	None	N
P/C	0.657	likely_pathogenic	0.615	pathogenic	-0.533	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/D	0.5345	ambiguous	0.5124	ambiguous	-0.751	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/E	0.3574	ambiguous	0.344	ambiguous	-0.813	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/F	0.7994	likely_pathogenic	0.7605	pathogenic	-0.732	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
P/G	0.3708	ambiguous	0.3498	ambiguous	-0.81	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/H	0.4178	ambiguous	0.3688	ambiguous	-0.288	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
P/I	0.5559	ambiguous	0.5232	ambiguous	-0.32	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/K	0.4637	ambiguous	0.4283	ambiguous	-0.58	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
P/L	0.3375	likely_benign	0.2933	benign	-0.32	Destabilizing	1.0	D	0.837	deleterious	N	0.472850042	None	None	N
P/M	0.5811	likely_pathogenic	0.5508	ambiguous	-0.509	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
P/N	0.4504	ambiguous	0.4195	ambiguous	-0.351	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/Q	0.308	likely_benign	0.2755	benign	-0.552	Destabilizing	1.0	D	0.807	deleterious	N	0.486657172	None	None	N
P/R	0.344	ambiguous	0.2989	benign	-0.081	Destabilizing	1.0	D	0.811	deleterious	N	0.468359413	None	None	N
P/S	0.2692	likely_benign	0.2379	benign	-0.65	Destabilizing	1.0	D	0.809	deleterious	N	0.489022686	None	None	N
P/T	0.2261	likely_benign	0.1995	benign	-0.617	Destabilizing	1.0	D	0.809	deleterious	N	0.456947553	None	None	N
P/V	0.4054	ambiguous	0.374	ambiguous	-0.396	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/W	0.8531	likely_pathogenic	0.8246	pathogenic	-0.853	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
P/Y	0.6536	likely_pathogenic	0.6177	pathogenic	-0.553	Destabilizing	1.0	D	0.785	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.