TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14339	43240;43241;43242	chr2:178633258;178633257;178633256	chr2:179497985;179497984;179497983
N2AB	12698	38317;38318;38319	chr2:178633258;178633257;178633256	chr2:179497985;179497984;179497983
N2A	11771	35536;35537;35538	chr2:178633258;178633257;178633256	chr2:179497985;179497984;179497983
N2B	5274	16045;16046;16047	chr2:178633258;178633257;178633256	chr2:179497985;179497984;179497983
Novex-1	5399	16420;16421;16422	chr2:178633258;178633257;178633256	chr2:179497985;179497984;179497983
Novex-2	5466	16621;16622;16623	chr2:178633258;178633257;178633256	chr2:179497985;179497984;179497983
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-94
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.1898
• 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/D	rs1353557766	None	0.997	N	0.618	0.176	0.194818534648	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1353557766	None	0.997	N	0.618	0.176	0.194818534648	gnomAD-4.0.0	6.57393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47063E-05	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
E/A	0.3072	likely_benign	0.2903	benign	-0.54	Destabilizing	0.997	D	0.733	deleterious	D	0.615268177	None	None	N
E/C	0.9437	likely_pathogenic	0.9374	pathogenic	-0.41	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/D	0.507	ambiguous	0.5085	ambiguous	-1.259	Destabilizing	0.997	D	0.618	neutral	N	0.416902333	None	None	N
E/F	0.9192	likely_pathogenic	0.9147	pathogenic	0.261	Stabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
E/G	0.4509	ambiguous	0.4668	ambiguous	-0.966	Destabilizing	0.999	D	0.769	deleterious	D	0.57803677	None	None	N
E/H	0.7299	likely_pathogenic	0.7306	pathogenic	-0.075	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
E/I	0.5866	likely_pathogenic	0.5431	ambiguous	0.635	Stabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
E/K	0.314	likely_benign	0.3206	benign	-0.657	Destabilizing	0.997	D	0.674	prob.neutral	D	0.576119949	None	None	N
E/L	0.7545	likely_pathogenic	0.7086	pathogenic	0.635	Stabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
E/M	0.6996	likely_pathogenic	0.6663	pathogenic	1.001	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/N	0.6331	likely_pathogenic	0.617	pathogenic	-1.264	Destabilizing	0.999	D	0.739	deleterious	None	None	None	None	N
E/P	0.9743	likely_pathogenic	0.972	pathogenic	0.266	Stabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
E/Q	0.205	likely_benign	0.2045	benign	-1.043	Destabilizing	0.999	D	0.714	prob.delet.	N	0.485425041	None	None	N
E/R	0.4665	ambiguous	0.4784	ambiguous	-0.369	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
E/S	0.3657	ambiguous	0.3555	ambiguous	-1.592	Destabilizing	0.998	D	0.704	prob.delet.	None	None	None	None	N
E/T	0.3786	ambiguous	0.341	ambiguous	-1.229	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
E/V	0.3828	ambiguous	0.3436	ambiguous	0.266	Stabilizing	0.999	D	0.823	deleterious	D	0.613180146	None	None	N
E/W	0.9748	likely_pathogenic	0.9757	pathogenic	0.466	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
E/Y	0.89	likely_pathogenic	0.8888	pathogenic	0.508	Stabilizing	1.0	D	0.882	deleterious	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.