TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13913	41962;41963;41964	chr2:178635587;178635586;178635585	chr2:179500314;179500313;179500312
N2AB	12272	37039;37040;37041	chr2:178635587;178635586;178635585	chr2:179500314;179500313;179500312
N2A	11345	34258;34259;34260	chr2:178635587;178635586;178635585	chr2:179500314;179500313;179500312
N2B	4848	14767;14768;14769	chr2:178635587;178635586;178635585	chr2:179500314;179500313;179500312
Novex-1	4973	15142;15143;15144	chr2:178635587;178635586;178635585	chr2:179500314;179500313;179500312
Novex-2	5040	15343;15344;15345	chr2:178635587;178635586;178635585	chr2:179500314;179500313;179500312
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-89
• Domain position: 38
• Structural Position: 58
• Q(SASA): 0.2746
• 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
I/V	None	None	0.041	N	0.507	0.09	0.377451072189	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
I/A	0.9864	likely_pathogenic	0.9896	pathogenic	-2.194	Highly Destabilizing	0.385	N	0.611	neutral	None	None	None	None	N
I/C	0.9919	likely_pathogenic	0.9944	pathogenic	-1.251	Destabilizing	0.981	D	0.705	prob.delet.	None	None	None	None	N
I/D	0.9969	likely_pathogenic	0.9971	pathogenic	-2.379	Highly Destabilizing	0.931	D	0.821	deleterious	None	None	None	None	N
I/E	0.9936	likely_pathogenic	0.994	pathogenic	-2.17	Highly Destabilizing	0.817	D	0.819	deleterious	None	None	None	None	N
I/F	0.6698	likely_pathogenic	0.7219	pathogenic	-1.315	Destabilizing	0.454	N	0.607	neutral	D	0.547609603	None	None	N
I/G	0.997	likely_pathogenic	0.9974	pathogenic	-2.703	Highly Destabilizing	0.817	D	0.819	deleterious	None	None	None	None	N
I/H	0.9909	likely_pathogenic	0.992	pathogenic	-2.077	Highly Destabilizing	0.981	D	0.805	deleterious	None	None	None	None	N
I/K	0.9878	likely_pathogenic	0.9895	pathogenic	-1.622	Destabilizing	0.817	D	0.819	deleterious	None	None	None	None	N
I/L	0.2355	likely_benign	0.3337	benign	-0.741	Destabilizing	0.001	N	0.254	neutral	N	0.434597695	None	None	N
I/M	0.3856	ambiguous	0.4572	ambiguous	-0.559	Destabilizing	0.624	D	0.58	neutral	D	0.548885324	None	None	N
I/N	0.9656	likely_pathogenic	0.9621	pathogenic	-1.903	Destabilizing	0.911	D	0.826	deleterious	D	0.549638229	None	None	N
I/P	0.9959	likely_pathogenic	0.9963	pathogenic	-1.205	Destabilizing	0.931	D	0.821	deleterious	None	None	None	None	N
I/Q	0.9901	likely_pathogenic	0.9916	pathogenic	-1.802	Destabilizing	0.931	D	0.811	deleterious	None	None	None	None	N
I/R	0.9864	likely_pathogenic	0.9886	pathogenic	-1.341	Destabilizing	0.817	D	0.834	deleterious	None	None	None	None	N
I/S	0.9866	likely_pathogenic	0.9873	pathogenic	-2.56	Highly Destabilizing	0.771	D	0.713	prob.delet.	D	0.548885324	None	None	N
I/T	0.986	likely_pathogenic	0.9877	pathogenic	-2.209	Highly Destabilizing	0.321	N	0.714	prob.delet.	D	0.548885324	None	None	N
I/V	0.4525	ambiguous	0.5174	ambiguous	-1.205	Destabilizing	0.041	N	0.507	neutral	N	0.475171451	None	None	N
I/W	0.9879	likely_pathogenic	0.9911	pathogenic	-1.678	Destabilizing	0.981	D	0.761	deleterious	None	None	None	None	N
I/Y	0.9408	likely_pathogenic	0.9468	pathogenic	-1.336	Destabilizing	0.817	D	0.695	prob.delet.	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.