TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19655	59188;59189;59190	chr2:178593245;178593244;178593243	chr2:179457972;179457971;179457970
N2AB	18014	54265;54266;54267	chr2:178593245;178593244;178593243	chr2:179457972;179457971;179457970
N2A	17087	51484;51485;51486	chr2:178593245;178593244;178593243	chr2:179457972;179457971;179457970
N2B	10590	31993;31994;31995	chr2:178593245;178593244;178593243	chr2:179457972;179457971;179457970
Novex-1	10715	32368;32369;32370	chr2:178593245;178593244;178593243	chr2:179457972;179457971;179457970
Novex-2	10782	32569;32570;32571	chr2:178593245;178593244;178593243	chr2:179457972;179457971;179457970
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-30
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1363
• 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
S/P	None	None	0.497	N	0.783	0.289	0.183819452728	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
S/A	0.0797	likely_benign	0.0758	benign	-1.079	Destabilizing	None	N	0.271	neutral	N	0.444519761	None	None	N
S/C	0.0759	likely_benign	0.0789	benign	-0.991	Destabilizing	0.883	D	0.748	deleterious	N	0.497047524	None	None	N
S/D	0.861	likely_pathogenic	0.8686	pathogenic	-2.032	Highly Destabilizing	0.567	D	0.765	deleterious	None	None	None	None	N
S/E	0.7807	likely_pathogenic	0.7789	pathogenic	-1.808	Destabilizing	0.272	N	0.755	deleterious	None	None	None	None	N
S/F	0.2068	likely_benign	0.1832	benign	-0.722	Destabilizing	0.497	N	0.785	deleterious	N	0.478115046	None	None	N
S/G	0.1794	likely_benign	0.1911	benign	-1.47	Destabilizing	0.157	N	0.717	prob.delet.	None	None	None	None	N
S/H	0.5168	ambiguous	0.4932	ambiguous	-1.689	Destabilizing	0.968	D	0.748	deleterious	None	None	None	None	N
S/I	0.2458	likely_benign	0.2409	benign	-0.072	Destabilizing	0.157	N	0.769	deleterious	None	None	None	None	N
S/K	0.8115	likely_pathogenic	0.8006	pathogenic	-0.564	Destabilizing	0.272	N	0.739	prob.delet.	None	None	None	None	N
S/L	0.0915	likely_benign	0.0882	benign	-0.072	Destabilizing	0.072	N	0.761	deleterious	None	None	None	None	N
S/M	0.1221	likely_benign	0.1316	benign	-0.341	Destabilizing	0.033	N	0.589	neutral	None	None	None	None	N
S/N	0.4078	ambiguous	0.4484	ambiguous	-1.351	Destabilizing	0.726	D	0.793	deleterious	None	None	None	None	N
S/P	0.9887	likely_pathogenic	0.9853	pathogenic	-0.375	Destabilizing	0.497	N	0.783	deleterious	N	0.494499469	None	None	N
S/Q	0.5942	likely_pathogenic	0.6038	pathogenic	-1.026	Destabilizing	0.726	D	0.777	deleterious	None	None	None	None	N
S/R	0.7329	likely_pathogenic	0.7201	pathogenic	-0.953	Destabilizing	0.567	D	0.781	deleterious	None	None	None	None	N
S/T	0.1005	likely_benign	0.1017	benign	-0.946	Destabilizing	0.124	N	0.739	prob.delet.	N	0.466223185	None	None	N
S/V	0.2221	likely_benign	0.2172	benign	-0.375	Destabilizing	0.157	N	0.759	deleterious	None	None	None	None	N
S/W	0.4079	ambiguous	0.3542	ambiguous	-1.064	Destabilizing	0.968	D	0.775	deleterious	None	None	None	None	N
S/Y	0.202	likely_benign	0.1772	benign	-0.62	Destabilizing	0.667	D	0.781	deleterious	N	0.480211202	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.