TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3218	9877;9878;9879	chr2:178766432;178766431;178766430	chr2:179631159;179631158;179631157
N2AB	3218	9877;9878;9879	chr2:178766432;178766431;178766430	chr2:179631159;179631158;179631157
N2A	3218	9877;9878;9879	chr2:178766432;178766431;178766430	chr2:179631159;179631158;179631157
N2B	3172	9739;9740;9741	chr2:178766432;178766431;178766430	chr2:179631159;179631158;179631157
Novex-1	3172	9739;9740;9741	chr2:178766432;178766431;178766430	chr2:179631159;179631158;179631157
Novex-2	3172	9739;9740;9741	chr2:178766432;178766431;178766430	chr2:179631159;179631158;179631157
Novex-3	3218	9877;9878;9879	chr2:178766432;178766431;178766430	chr2:179631159;179631158;179631157

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-22
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.1085
• 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/C	None	None	0.999	D	0.871	0.428	0.37281450598	gnomAD-4.0.0	6.8408E-07	None	None	None	None	N	None	0	2.23624E-05	None	0	0	None	0	0	0	0	0
Y/S	None	None	0.989	D	0.881	0.411	0.495970961353	gnomAD-4.0.0	6.8408E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-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	0.9989	likely_pathogenic	0.9993	pathogenic	-3.193	Highly Destabilizing	0.944	D	0.836	deleterious	None	None	None	None	N
Y/C	0.992	likely_pathogenic	0.9937	pathogenic	-2.343	Highly Destabilizing	0.999	D	0.871	deleterious	D	0.529891844	None	None	N
Y/D	0.9987	likely_pathogenic	0.9994	pathogenic	-3.711	Highly Destabilizing	0.996	D	0.881	deleterious	D	0.529891844	None	None	N
Y/E	0.9996	likely_pathogenic	0.9998	pathogenic	-3.491	Highly Destabilizing	0.997	D	0.882	deleterious	None	None	None	None	N
Y/F	0.4328	ambiguous	0.4417	ambiguous	-1.176	Destabilizing	0.039	N	0.413	neutral	N	0.40983847	None	None	N
Y/G	0.9965	likely_pathogenic	0.9975	pathogenic	-3.64	Highly Destabilizing	0.992	D	0.886	deleterious	None	None	None	None	N
Y/H	0.995	likely_pathogenic	0.9968	pathogenic	-2.386	Highly Destabilizing	0.996	D	0.733	prob.delet.	D	0.529891844	None	None	N
Y/I	0.9733	likely_pathogenic	0.9766	pathogenic	-1.7	Destabilizing	0.968	D	0.819	deleterious	None	None	None	None	N
Y/K	0.9994	likely_pathogenic	0.9997	pathogenic	-2.43	Highly Destabilizing	0.992	D	0.883	deleterious	None	None	None	None	N
Y/L	0.9551	likely_pathogenic	0.9537	pathogenic	-1.7	Destabilizing	0.895	D	0.75	deleterious	None	None	None	None	N
Y/M	0.9895	likely_pathogenic	0.9917	pathogenic	-1.65	Destabilizing	0.998	D	0.816	deleterious	None	None	None	None	N
Y/N	0.9929	likely_pathogenic	0.996	pathogenic	-3.301	Highly Destabilizing	0.996	D	0.873	deleterious	D	0.529891844	None	None	N
Y/P	0.9997	likely_pathogenic	0.9998	pathogenic	-2.215	Highly Destabilizing	0.997	D	0.893	deleterious	None	None	None	None	N
Y/Q	0.9997	likely_pathogenic	0.9998	pathogenic	-3.002	Highly Destabilizing	0.997	D	0.812	deleterious	None	None	None	None	N
Y/R	0.9985	likely_pathogenic	0.9991	pathogenic	-2.231	Highly Destabilizing	0.992	D	0.868	deleterious	None	None	None	None	N
Y/S	0.9978	likely_pathogenic	0.9987	pathogenic	-3.671	Highly Destabilizing	0.989	D	0.881	deleterious	D	0.529891844	None	None	N
Y/T	0.9988	likely_pathogenic	0.9992	pathogenic	-3.317	Highly Destabilizing	0.992	D	0.883	deleterious	None	None	None	None	N
Y/V	0.9658	likely_pathogenic	0.9707	pathogenic	-2.215	Highly Destabilizing	0.895	D	0.784	deleterious	None	None	None	None	N
Y/W	0.9518	likely_pathogenic	0.9364	pathogenic	-0.507	Destabilizing	0.999	D	0.729	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.