TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30970	93133;93134;93135	chr2:178548718;178548717;178548716	chr2:179413445;179413444;179413443
N2AB	29329	88210;88211;88212	chr2:178548718;178548717;178548716	chr2:179413445;179413444;179413443
N2A	28402	85429;85430;85431	chr2:178548718;178548717;178548716	chr2:179413445;179413444;179413443
N2B	21905	65938;65939;65940	chr2:178548718;178548717;178548716	chr2:179413445;179413444;179413443
Novex-1	22030	66313;66314;66315	chr2:178548718;178548717;178548716	chr2:179413445;179413444;179413443
Novex-2	22097	66514;66515;66516	chr2:178548718;178548717;178548716	chr2:179413445;179413444;179413443
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-150
• Domain position: 44
• Structural Position: 102
• Q(SASA): 0.3072
• 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
A/T	rs766530422	-0.768	0.925	N	0.455	0.171	0.311079019809	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
A/T	rs766530422	-0.768	0.925	N	0.455	0.171	0.311079019809	gnomAD-4.0.0	3.18245E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86541E-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
A/C	0.5247	ambiguous	0.5117	ambiguous	-1.089	Destabilizing	1.0	D	0.511	neutral	None	None	None	None	N
A/D	0.9045	likely_pathogenic	0.9161	pathogenic	-0.976	Destabilizing	0.989	D	0.641	neutral	D	0.533078187	None	None	N
A/E	0.8675	likely_pathogenic	0.8816	pathogenic	-1.016	Destabilizing	0.991	D	0.589	neutral	None	None	None	None	N
A/F	0.7653	likely_pathogenic	0.781	pathogenic	-1.034	Destabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	N
A/G	0.196	likely_benign	0.1949	benign	-1.08	Destabilizing	0.071	N	0.322	neutral	N	0.498984256	None	None	N
A/H	0.8993	likely_pathogenic	0.9166	pathogenic	-1.275	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
A/I	0.608	likely_pathogenic	0.599	pathogenic	-0.34	Destabilizing	0.983	D	0.585	neutral	None	None	None	None	N
A/K	0.9404	likely_pathogenic	0.9494	pathogenic	-1.155	Destabilizing	0.991	D	0.593	neutral	None	None	None	None	N
A/L	0.5378	ambiguous	0.5176	ambiguous	-0.34	Destabilizing	0.942	D	0.505	neutral	None	None	None	None	N
A/M	0.5437	ambiguous	0.546	ambiguous	-0.386	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
A/N	0.8149	likely_pathogenic	0.843	pathogenic	-0.924	Destabilizing	0.991	D	0.654	neutral	None	None	None	None	N
A/P	0.9172	likely_pathogenic	0.9213	pathogenic	-0.464	Destabilizing	0.994	D	0.621	neutral	N	0.494784591	None	None	N
A/Q	0.8629	likely_pathogenic	0.8725	pathogenic	-1.068	Destabilizing	0.996	D	0.625	neutral	None	None	None	None	N
A/R	0.9123	likely_pathogenic	0.9164	pathogenic	-0.846	Destabilizing	0.996	D	0.624	neutral	None	None	None	None	N
A/S	0.1683	likely_benign	0.1814	benign	-1.286	Destabilizing	0.689	D	0.334	neutral	N	0.501139127	None	None	N
A/T	0.1775	likely_benign	0.1961	benign	-1.219	Destabilizing	0.925	D	0.455	neutral	N	0.489383338	None	None	N
A/V	0.2628	likely_benign	0.2528	benign	-0.464	Destabilizing	0.433	N	0.322	neutral	N	0.465407613	None	None	N
A/W	0.9426	likely_pathogenic	0.942	pathogenic	-1.345	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
A/Y	0.8318	likely_pathogenic	0.8376	pathogenic	-0.934	Destabilizing	0.999	D	0.686	prob.neutral	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.