TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33252	99979;99980;99981	chr2:178537453;178537452;178537451	chr2:179402180;179402179;179402178
N2AB	31611	95056;95057;95058	chr2:178537453;178537452;178537451	chr2:179402180;179402179;179402178
N2A	30684	92275;92276;92277	chr2:178537453;178537452;178537451	chr2:179402180;179402179;179402178
N2B	24187	72784;72785;72786	chr2:178537453;178537452;178537451	chr2:179402180;179402179;179402178
Novex-1	24312	73159;73160;73161	chr2:178537453;178537452;178537451	chr2:179402180;179402179;179402178
Novex-2	24379	73360;73361;73362	chr2:178537453;178537452;178537451	chr2:179402180;179402179;179402178
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-157
• Domain position: 50
• Structural Position: 136
• Q(SASA): 0.1139
• 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
T/I	None	None	1.0	N	0.813	0.428	0.284539287134	gnomAD-4.0.0	1.36887E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16036E-05	1.65706E-05

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
T/A	0.3913	ambiguous	0.3565	ambiguous	-1.968	Destabilizing	0.997	D	0.662	neutral	N	0.485605874	None	None	N
T/C	0.7573	likely_pathogenic	0.7616	pathogenic	-1.667	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/D	0.9898	likely_pathogenic	0.9829	pathogenic	-1.927	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/E	0.9909	likely_pathogenic	0.9858	pathogenic	-1.675	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/F	0.9694	likely_pathogenic	0.9632	pathogenic	-1.025	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
T/G	0.8147	likely_pathogenic	0.7575	pathogenic	-2.29	Highly Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/H	0.9589	likely_pathogenic	0.9434	pathogenic	-1.8	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
T/I	0.8756	likely_pathogenic	0.8412	pathogenic	-1.048	Destabilizing	1.0	D	0.813	deleterious	N	0.511600397	None	None	N
T/K	0.9859	likely_pathogenic	0.9792	pathogenic	-1.104	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/L	0.6674	likely_pathogenic	0.638	pathogenic	-1.048	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
T/M	0.5576	ambiguous	0.5307	ambiguous	-1.516	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
T/N	0.8525	likely_pathogenic	0.8065	pathogenic	-1.713	Destabilizing	1.0	D	0.811	deleterious	N	0.461719275	None	None	N
T/P	0.9671	likely_pathogenic	0.9619	pathogenic	-1.342	Destabilizing	1.0	D	0.808	deleterious	N	0.45488242	None	None	N
T/Q	0.9573	likely_pathogenic	0.9426	pathogenic	-1.254	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
T/R	0.9749	likely_pathogenic	0.9656	pathogenic	-1.452	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
T/S	0.3042	likely_benign	0.2976	benign	-2.095	Highly Destabilizing	0.929	D	0.531	neutral	N	0.469193627	None	None	N
T/V	0.707	likely_pathogenic	0.6763	pathogenic	-1.342	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
T/W	0.9947	likely_pathogenic	0.9937	pathogenic	-1.207	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
T/Y	0.9798	likely_pathogenic	0.9737	pathogenic	-1.096	Destabilizing	1.0	D	0.825	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.