TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2144	6655;6656;6657	chr2:178775434;178775433;178775432	chr2:179640161;179640160;179640159
N2AB	2144	6655;6656;6657	chr2:178775434;178775433;178775432	chr2:179640161;179640160;179640159
N2A	2144	6655;6656;6657	chr2:178775434;178775433;178775432	chr2:179640161;179640160;179640159
N2B	2098	6517;6518;6519	chr2:178775434;178775433;178775432	chr2:179640161;179640160;179640159
Novex-1	2098	6517;6518;6519	chr2:178775434;178775433;178775432	chr2:179640161;179640160;179640159
Novex-2	2098	6517;6518;6519	chr2:178775434;178775433;178775432	chr2:179640161;179640160;179640159
Novex-3	2144	6655;6656;6657	chr2:178775434;178775433;178775432	chr2:179640161;179640160;179640159

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-10
• Domain position: 67
• Structural Position: 148
• Q(SASA): 0.8163
• 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
E/K	rs747447866	0.962	0.334	D	0.561	0.288	0.32580497728	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs747447866	0.962	0.334	D	0.561	0.288	0.32580497728	gnomAD-4.0.0	1.59074E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
E/A	0.1447	likely_benign	0.1472	benign	-0.037	Destabilizing	0.334	N	0.604	neutral	N	0.507166245	None	None	N
E/C	0.9085	likely_pathogenic	0.9177	pathogenic	0.179	Stabilizing	0.982	D	0.789	deleterious	None	None	None	None	N
E/D	0.0865	likely_benign	0.0871	benign	-0.135	Destabilizing	0.001	N	0.176	neutral	N	0.507638781	None	None	N
E/F	0.7994	likely_pathogenic	0.8338	pathogenic	-0.176	Destabilizing	0.982	D	0.749	deleterious	None	None	None	None	N
E/G	0.202	likely_benign	0.2023	benign	-0.15	Destabilizing	0.334	N	0.567	neutral	N	0.511614229	None	None	N
E/H	0.6001	likely_pathogenic	0.607	pathogenic	0.226	Stabilizing	0.947	D	0.669	neutral	None	None	None	None	N
E/I	0.4631	ambiguous	0.4849	ambiguous	0.199	Stabilizing	0.826	D	0.772	deleterious	None	None	None	None	N
E/K	0.267	likely_benign	0.2535	benign	0.614	Stabilizing	0.334	N	0.561	neutral	D	0.549173317	None	None	N
E/L	0.4541	ambiguous	0.4848	ambiguous	0.199	Stabilizing	0.7	D	0.761	deleterious	None	None	None	None	N
E/M	0.5414	ambiguous	0.5536	ambiguous	0.204	Stabilizing	0.982	D	0.717	prob.delet.	None	None	None	None	N
E/N	0.2338	likely_benign	0.2397	benign	0.472	Stabilizing	0.539	D	0.657	neutral	None	None	None	None	N
E/P	0.7543	likely_pathogenic	0.8065	pathogenic	0.138	Stabilizing	0.826	D	0.717	prob.delet.	None	None	None	None	N
E/Q	0.2141	likely_benign	0.2047	benign	0.47	Stabilizing	0.638	D	0.638	neutral	N	0.513788776	None	None	N
E/R	0.4336	ambiguous	0.4357	ambiguous	0.693	Stabilizing	0.7	D	0.699	prob.neutral	None	None	None	None	N
E/S	0.1752	likely_benign	0.1794	benign	0.317	Stabilizing	0.25	N	0.571	neutral	None	None	None	None	N
E/T	0.2465	likely_benign	0.251	benign	0.414	Stabilizing	0.7	D	0.659	neutral	None	None	None	None	N
E/V	0.2885	likely_benign	0.3031	benign	0.138	Stabilizing	0.781	D	0.726	prob.delet.	D	0.633217716	None	None	N
E/W	0.9378	likely_pathogenic	0.9471	pathogenic	-0.153	Destabilizing	0.982	D	0.793	deleterious	None	None	None	None	N
E/Y	0.7211	likely_pathogenic	0.7478	pathogenic	0.046	Stabilizing	0.982	D	0.731	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.