TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32424	97495;97496;97497	chr2:178542486;178542485;178542484	chr2:179407213;179407212;179407211
N2AB	30783	92572;92573;92574	chr2:178542486;178542485;178542484	chr2:179407213;179407212;179407211
N2A	29856	89791;89792;89793	chr2:178542486;178542485;178542484	chr2:179407213;179407212;179407211
N2B	23359	70300;70301;70302	chr2:178542486;178542485;178542484	chr2:179407213;179407212;179407211
Novex-1	23484	70675;70676;70677	chr2:178542486;178542485;178542484	chr2:179407213;179407212;179407211
Novex-2	23551	70876;70877;70878	chr2:178542486;178542485;178542484	chr2:179407213;179407212;179407211
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-124
• Domain position: 26
• Structural Position: 27
• Q(SASA): 0.1614
• 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	0.085	D	0.683	0.657	0.679066282414	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
P/A	0.6629	likely_pathogenic	0.5533	ambiguous	-1.942	Destabilizing	0.928	D	0.733	prob.delet.	D	0.620898908	None	None	N
P/C	0.956	likely_pathogenic	0.933	pathogenic	-1.364	Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
P/D	0.9965	likely_pathogenic	0.9949	pathogenic	-2.706	Highly Destabilizing	0.992	D	0.845	deleterious	None	None	None	None	N
P/E	0.9903	likely_pathogenic	0.9846	pathogenic	-2.605	Highly Destabilizing	0.983	D	0.812	deleterious	None	None	None	None	N
P/F	0.9982	likely_pathogenic	0.9969	pathogenic	-1.334	Destabilizing	0.999	D	0.896	deleterious	None	None	None	None	N
P/G	0.9715	likely_pathogenic	0.957	pathogenic	-2.366	Highly Destabilizing	0.983	D	0.847	deleterious	None	None	None	None	N
P/H	0.9904	likely_pathogenic	0.9846	pathogenic	-2.244	Highly Destabilizing	0.997	D	0.885	deleterious	D	0.632214255	None	None	N
P/I	0.9828	likely_pathogenic	0.9693	pathogenic	-0.808	Destabilizing	0.992	D	0.881	deleterious	None	None	None	None	N
P/K	0.9956	likely_pathogenic	0.9931	pathogenic	-1.812	Destabilizing	0.895	D	0.764	deleterious	None	None	None	None	N
P/L	0.9336	likely_pathogenic	0.8836	pathogenic	-0.808	Destabilizing	0.978	D	0.887	deleterious	D	0.643852848	None	None	N
P/M	0.9828	likely_pathogenic	0.9703	pathogenic	-0.609	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
P/N	0.9951	likely_pathogenic	0.9929	pathogenic	-1.813	Destabilizing	0.983	D	0.89	deleterious	None	None	None	None	N
P/Q	0.9834	likely_pathogenic	0.9707	pathogenic	-1.839	Destabilizing	0.983	D	0.847	deleterious	None	None	None	None	N
P/R	0.9863	likely_pathogenic	0.9773	pathogenic	-1.423	Destabilizing	0.085	N	0.683	prob.neutral	D	0.632214255	None	None	N
P/S	0.9167	likely_pathogenic	0.8731	pathogenic	-2.268	Highly Destabilizing	0.978	D	0.818	deleterious	D	0.589617401	None	None	N
P/T	0.8985	likely_pathogenic	0.8443	pathogenic	-2.06	Highly Destabilizing	0.978	D	0.814	deleterious	D	0.653139434	None	None	N
P/V	0.933	likely_pathogenic	0.8892	pathogenic	-1.157	Destabilizing	0.992	D	0.885	deleterious	None	None	None	None	N
P/W	0.9992	likely_pathogenic	0.9986	pathogenic	-1.831	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
P/Y	0.9983	likely_pathogenic	0.9971	pathogenic	-1.502	Destabilizing	0.999	D	0.896	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.