TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31137	93634;93635;93636	chr2:178548217;178548216;178548215	chr2:179412944;179412943;179412942
N2AB	29496	88711;88712;88713	chr2:178548217;178548216;178548215	chr2:179412944;179412943;179412942
N2A	28569	85930;85931;85932	chr2:178548217;178548216;178548215	chr2:179412944;179412943;179412942
N2B	22072	66439;66440;66441	chr2:178548217;178548216;178548215	chr2:179412944;179412943;179412942
Novex-1	22197	66814;66815;66816	chr2:178548217;178548216;178548215	chr2:179412944;179412943;179412942
Novex-2	22264	67015;67016;67017	chr2:178548217;178548216;178548215	chr2:179412944;179412943;179412942
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: Fn3-115
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1506
• 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/T	None	None	0.998	D	0.785	0.709	0.572452295634	gnomAD-4.0.0	3.42089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49722E-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	0.8772	likely_pathogenic	0.8537	pathogenic	-2.05	Highly Destabilizing	0.992	D	0.697	prob.neutral	D	0.584615167	None	None	N
P/C	0.9904	likely_pathogenic	0.9884	pathogenic	-1.429	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/D	0.9976	likely_pathogenic	0.9978	pathogenic	-3.001	Highly Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
P/E	0.9959	likely_pathogenic	0.9953	pathogenic	-2.871	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9994	pathogenic	-1.263	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
P/G	0.9833	likely_pathogenic	0.9814	pathogenic	-2.471	Highly Destabilizing	0.997	D	0.807	deleterious	None	None	None	None	N
P/H	0.9959	likely_pathogenic	0.9947	pathogenic	-2.342	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.636296803	None	None	N
P/I	0.9958	likely_pathogenic	0.9947	pathogenic	-0.889	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
P/K	0.9983	likely_pathogenic	0.9978	pathogenic	-1.803	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
P/L	0.979	likely_pathogenic	0.9711	pathogenic	-0.889	Destabilizing	0.999	D	0.885	deleterious	D	0.635287782	None	None	N
P/M	0.9952	likely_pathogenic	0.9939	pathogenic	-0.694	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/N	0.9968	likely_pathogenic	0.9966	pathogenic	-1.928	Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
P/Q	0.9941	likely_pathogenic	0.9933	pathogenic	-1.885	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/R	0.9947	likely_pathogenic	0.9932	pathogenic	-1.47	Destabilizing	0.999	D	0.881	deleterious	D	0.619843474	None	None	N
P/S	0.9687	likely_pathogenic	0.9673	pathogenic	-2.35	Highly Destabilizing	0.957	D	0.544	neutral	D	0.551940672	None	None	N
P/T	0.968	likely_pathogenic	0.9579	pathogenic	-2.125	Highly Destabilizing	0.998	D	0.785	deleterious	D	0.594103558	None	None	N
P/V	0.9837	likely_pathogenic	0.9794	pathogenic	-1.253	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9996	pathogenic	-1.863	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/Y	0.9993	likely_pathogenic	0.9991	pathogenic	-1.573	Destabilizing	1.0	D	0.902	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.