TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18469	55630;55631;55632	chr2:178601685;178601684;178601683	chr2:179466412;179466411;179466410
N2AB	16828	50707;50708;50709	chr2:178601685;178601684;178601683	chr2:179466412;179466411;179466410
N2A	15901	47926;47927;47928	chr2:178601685;178601684;178601683	chr2:179466412;179466411;179466410
N2B	9404	28435;28436;28437	chr2:178601685;178601684;178601683	chr2:179466412;179466411;179466410
Novex-1	9529	28810;28811;28812	chr2:178601685;178601684;178601683	chr2:179466412;179466411;179466410
Novex-2	9596	29011;29012;29013	chr2:178601685;178601684;178601683	chr2:179466412;179466411;179466410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-115
• Domain position: 88
• Structural Position: 168
• Q(SASA): 0.6293
• Predicted PPI site: I

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
T/P	rs1044328956	-0.217	0.998	N	0.684	0.429	0.622259118589	gnomAD-2.1.1	2.09E-05	None	None	None	None	I	None	0	1.2282E-04	None	1.05686E-04	0	None	0	None	0	0	0
T/P	rs1044328956	-0.217	0.998	N	0.684	0.429	0.622259118589	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	1.96721E-04	0	0	0	None	0	0	0	0	0
T/P	rs1044328956	-0.217	0.998	N	0.684	0.429	0.622259118589	gnomAD-4.0.0	8.10793E-06	None	None	None	None	I	None	0	1.90338E-04	None	0	0	None	0	0	8.4974E-07	0	1.61368E-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
T/A	0.1262	likely_benign	0.1376	benign	-0.484	Destabilizing	0.954	D	0.574	neutral	N	0.512628344	None	None	I
T/C	0.5366	ambiguous	0.5361	ambiguous	-0.214	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
T/D	0.625	likely_pathogenic	0.6655	pathogenic	-0.199	Destabilizing	0.985	D	0.619	neutral	None	None	None	None	I
T/E	0.4267	ambiguous	0.4631	ambiguous	-0.275	Destabilizing	0.97	D	0.631	neutral	None	None	None	None	I
T/F	0.3238	likely_benign	0.3454	ambiguous	-0.928	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	I
T/G	0.4467	ambiguous	0.4746	ambiguous	-0.632	Destabilizing	0.985	D	0.634	neutral	None	None	None	None	I
T/H	0.3116	likely_benign	0.3107	benign	-1.019	Destabilizing	0.092	N	0.371	neutral	None	None	None	None	I
T/I	0.1837	likely_benign	0.1864	benign	-0.208	Destabilizing	0.998	D	0.679	prob.neutral	D	0.528752589	None	None	I
T/K	0.2434	likely_benign	0.2428	benign	-0.519	Destabilizing	0.97	D	0.626	neutral	None	None	None	None	I
T/L	0.1486	likely_benign	0.1661	benign	-0.208	Destabilizing	0.985	D	0.611	neutral	None	None	None	None	I
T/M	0.0855	likely_benign	0.0902	benign	0.178	Stabilizing	1.0	D	0.64	neutral	None	None	None	None	I
T/N	0.1936	likely_benign	0.2067	benign	-0.274	Destabilizing	0.961	D	0.543	neutral	N	0.502523726	None	None	I
T/P	0.4751	ambiguous	0.5768	pathogenic	-0.271	Destabilizing	0.998	D	0.684	prob.neutral	N	0.492181379	None	None	I
T/Q	0.2494	likely_benign	0.2625	benign	-0.576	Destabilizing	0.996	D	0.684	prob.neutral	None	None	None	None	I
T/R	0.2123	likely_benign	0.2299	benign	-0.191	Destabilizing	0.991	D	0.638	neutral	None	None	None	None	I
T/S	0.1597	likely_benign	0.1657	benign	-0.46	Destabilizing	0.98	D	0.583	neutral	N	0.471107008	None	None	I
T/V	0.1435	likely_benign	0.1427	benign	-0.271	Destabilizing	0.995	D	0.523	neutral	None	None	None	None	I
T/W	0.6783	likely_pathogenic	0.7103	pathogenic	-0.898	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
T/Y	0.3559	ambiguous	0.3779	ambiguous	-0.642	Destabilizing	0.991	D	0.645	neutral	None	None	None	None	I

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.