TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35007	105244;105245;105246	chr2:178531596;178531595;178531594	chr2:179396323;179396322;179396321
N2AB	33366	100321;100322;100323	chr2:178531596;178531595;178531594	chr2:179396323;179396322;179396321
N2A	32439	97540;97541;97542	chr2:178531596;178531595;178531594	chr2:179396323;179396322;179396321
N2B	25942	78049;78050;78051	chr2:178531596;178531595;178531594	chr2:179396323;179396322;179396321
Novex-1	26067	78424;78425;78426	chr2:178531596;178531595;178531594	chr2:179396323;179396322;179396321
Novex-2	26134	78625;78626;78627	chr2:178531596;178531595;178531594	chr2:179396323;179396322;179396321
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-163
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.7616
• 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
D/Y	None	None	0.741	N	0.391	0.305	0.370051654043	gnomAD-4.0.0	1.5909E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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
D/A	0.0994	likely_benign	0.116	benign	-0.121	Destabilizing	0.062	N	0.395	neutral	N	0.44058566	None	None	N
D/C	0.5268	ambiguous	0.596	pathogenic	0.132	Stabilizing	0.935	D	0.458	neutral	None	None	None	None	N
D/E	0.0708	likely_benign	0.0815	benign	-0.165	Destabilizing	None	N	0.16	neutral	N	0.37164565	None	None	N
D/F	0.5634	ambiguous	0.6511	pathogenic	-0.25	Destabilizing	0.791	D	0.391	neutral	None	None	None	None	N
D/G	0.1099	likely_benign	0.1321	benign	-0.254	Destabilizing	0.117	N	0.389	neutral	N	0.503962348	None	None	N
D/H	0.23	likely_benign	0.2785	benign	0.094	Stabilizing	0.484	N	0.328	neutral	N	0.461074165	None	None	N
D/I	0.2819	likely_benign	0.3394	benign	0.166	Stabilizing	0.555	D	0.401	neutral	None	None	None	None	N
D/K	0.1911	likely_benign	0.2378	benign	0.447	Stabilizing	0.081	N	0.37	neutral	None	None	None	None	N
D/L	0.2902	likely_benign	0.3525	ambiguous	0.166	Stabilizing	0.38	N	0.381	neutral	None	None	None	None	N
D/M	0.4349	ambiguous	0.5144	ambiguous	0.233	Stabilizing	0.935	D	0.386	neutral	None	None	None	None	N
D/N	0.0864	likely_benign	0.0997	benign	0.311	Stabilizing	0.117	N	0.406	neutral	N	0.490955766	None	None	N
D/P	0.5576	ambiguous	0.6347	pathogenic	0.09	Stabilizing	0.555	D	0.333	neutral	None	None	None	None	N
D/Q	0.1826	likely_benign	0.2224	benign	0.307	Stabilizing	0.081	N	0.358	neutral	None	None	None	None	N
D/R	0.2393	likely_benign	0.296	benign	0.577	Stabilizing	0.235	N	0.371	neutral	None	None	None	None	N
D/S	0.0798	likely_benign	0.0894	benign	0.183	Stabilizing	0.081	N	0.377	neutral	None	None	None	None	N
D/T	0.1452	likely_benign	0.1676	benign	0.284	Stabilizing	0.149	N	0.394	neutral	None	None	None	None	N
D/V	0.1701	likely_benign	0.2005	benign	0.09	Stabilizing	0.317	N	0.398	neutral	N	0.511101751	None	None	N
D/W	0.8037	likely_pathogenic	0.8606	pathogenic	-0.197	Destabilizing	0.935	D	0.537	neutral	None	None	None	None	N
D/Y	0.2646	likely_benign	0.3128	benign	-0.028	Destabilizing	0.741	D	0.391	neutral	N	0.461327655	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.