TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3230	9913;9914;9915	chr2:178766396;178766395;178766394	chr2:179631123;179631122;179631121
N2AB	3230	9913;9914;9915	chr2:178766396;178766395;178766394	chr2:179631123;179631122;179631121
N2A	3230	9913;9914;9915	chr2:178766396;178766395;178766394	chr2:179631123;179631122;179631121
N2B	3184	9775;9776;9777	chr2:178766396;178766395;178766394	chr2:179631123;179631122;179631121
Novex-1	3184	9775;9776;9777	chr2:178766396;178766395;178766394	chr2:179631123;179631122;179631121
Novex-2	3184	9775;9776;9777	chr2:178766396;178766395;178766394	chr2:179631123;179631122;179631121
Novex-3	3230	9913;9914;9915	chr2:178766396;178766395;178766394	chr2:179631123;179631122;179631121

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-22
• Domain position: 84
• Structural Position: 173
• Q(SASA): 0.4936
• 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/I	None	None	0.012	N	0.294	0.182	0.200317383148	gnomAD-4.0.0	1.20273E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31513E-06	0	0
T/N	None	None	0.022	N	0.193	0.131	0.139678290688	gnomAD-4.0.0	1.20273E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31513E-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
T/A	0.178	likely_benign	0.1428	benign	-1.029	Destabilizing	0.454	N	0.455	neutral	N	0.32862299	None	None	I
T/C	0.7061	likely_pathogenic	0.605	pathogenic	-0.633	Destabilizing	0.998	D	0.528	neutral	None	None	None	None	I
T/D	0.7259	likely_pathogenic	0.6743	pathogenic	-0.4	Destabilizing	0.728	D	0.522	neutral	None	None	None	None	I
T/E	0.6266	likely_pathogenic	0.5637	ambiguous	-0.29	Destabilizing	0.842	D	0.533	neutral	None	None	None	None	I
T/F	0.4123	ambiguous	0.307	benign	-0.781	Destabilizing	0.949	D	0.592	neutral	None	None	None	None	I
T/G	0.6203	likely_pathogenic	0.5454	ambiguous	-1.382	Destabilizing	0.842	D	0.532	neutral	None	None	None	None	I
T/H	0.4066	ambiguous	0.326	benign	-1.465	Destabilizing	0.037	N	0.345	neutral	None	None	None	None	I
T/I	0.2097	likely_benign	0.1657	benign	-0.139	Destabilizing	0.012	N	0.294	neutral	N	0.34263545	None	None	I
T/K	0.334	likely_benign	0.2873	benign	-0.477	Destabilizing	0.842	D	0.516	neutral	None	None	None	None	I
T/L	0.187	likely_benign	0.1298	benign	-0.139	Destabilizing	0.525	D	0.432	neutral	None	None	None	None	I
T/M	0.1243	likely_benign	0.1026	benign	-0.095	Destabilizing	0.949	D	0.561	neutral	None	None	None	None	I
T/N	0.2319	likely_benign	0.1829	benign	-0.744	Destabilizing	0.022	N	0.193	neutral	N	0.351408224	None	None	I
T/P	0.4504	ambiguous	0.371	ambiguous	-0.403	Destabilizing	0.989	D	0.625	neutral	N	0.343733911	None	None	I
T/Q	0.3949	ambiguous	0.3234	benign	-0.719	Destabilizing	0.974	D	0.625	neutral	None	None	None	None	I
T/R	0.2974	likely_benign	0.25	benign	-0.465	Destabilizing	0.949	D	0.609	neutral	None	None	None	None	I
T/S	0.2309	likely_benign	0.1854	benign	-1.097	Destabilizing	0.625	D	0.511	neutral	N	0.346673316	None	None	I
T/V	0.1918	likely_benign	0.1495	benign	-0.403	Destabilizing	0.016	N	0.187	neutral	None	None	None	None	I
T/W	0.8108	likely_pathogenic	0.7257	pathogenic	-0.751	Destabilizing	0.998	D	0.552	neutral	None	None	None	None	I
T/Y	0.4909	ambiguous	0.3626	ambiguous	-0.461	Destabilizing	0.949	D	0.597	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.