TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22389	67390;67391;67392	chr2:178580122;178580121;178580120	chr2:179444849;179444848;179444847
N2AB	20748	62467;62468;62469	chr2:178580122;178580121;178580120	chr2:179444849;179444848;179444847
N2A	19821	59686;59687;59688	chr2:178580122;178580121;178580120	chr2:179444849;179444848;179444847
N2B	13324	40195;40196;40197	chr2:178580122;178580121;178580120	chr2:179444849;179444848;179444847
Novex-1	13449	40570;40571;40572	chr2:178580122;178580121;178580120	chr2:179444849;179444848;179444847
Novex-2	13516	40771;40772;40773	chr2:178580122;178580121;178580120	chr2:179444849;179444848;179444847
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-50
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1177
• 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
Y/H	None	None	1.0	D	0.796	0.877	0.754030569082	gnomAD-4.0.0	1.36877E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99677E-07	1.15953E-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
Y/A	0.9968	likely_pathogenic	0.9975	pathogenic	-3.594	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
Y/C	0.9379	likely_pathogenic	0.9573	pathogenic	-2.171	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.644672578	None	None	N
Y/D	0.9966	likely_pathogenic	0.9975	pathogenic	-3.935	Highly Destabilizing	1.0	D	0.906	deleterious	D	0.670614298	None	None	N
Y/E	0.9994	likely_pathogenic	0.9995	pathogenic	-3.732	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/F	0.3098	likely_benign	0.3322	benign	-1.339	Destabilizing	0.999	D	0.659	neutral	D	0.571512147	None	None	N
Y/G	0.9909	likely_pathogenic	0.9931	pathogenic	-3.989	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
Y/H	0.9758	likely_pathogenic	0.9796	pathogenic	-2.57	Highly Destabilizing	1.0	D	0.796	deleterious	D	0.644672578	None	None	N
Y/I	0.9874	likely_pathogenic	0.9893	pathogenic	-2.254	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
Y/K	0.9989	likely_pathogenic	0.9991	pathogenic	-2.523	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/L	0.9671	likely_pathogenic	0.9741	pathogenic	-2.254	Highly Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
Y/M	0.9905	likely_pathogenic	0.9919	pathogenic	-2.04	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/N	0.9821	likely_pathogenic	0.9852	pathogenic	-3.276	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.670614298	None	None	N
Y/P	0.9996	likely_pathogenic	0.9997	pathogenic	-2.719	Highly Destabilizing	1.0	D	0.932	deleterious	None	None	None	None	N
Y/Q	0.9988	likely_pathogenic	0.9991	pathogenic	-3.05	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/R	0.9952	likely_pathogenic	0.996	pathogenic	-2.194	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/S	0.9877	likely_pathogenic	0.9909	pathogenic	-3.598	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.670614298	None	None	N
Y/T	0.995	likely_pathogenic	0.9963	pathogenic	-3.282	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/V	0.9712	likely_pathogenic	0.9764	pathogenic	-2.719	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
Y/W	0.9186	likely_pathogenic	0.9234	pathogenic	-0.59	Destabilizing	1.0	D	0.788	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.