TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21756	65491;65492;65493	chr2:178584285;178584284;178584283	chr2:179449012;179449011;179449010
N2AB	20115	60568;60569;60570	chr2:178584285;178584284;178584283	chr2:179449012;179449011;179449010
N2A	19188	57787;57788;57789	chr2:178584285;178584284;178584283	chr2:179449012;179449011;179449010
N2B	12691	38296;38297;38298	chr2:178584285;178584284;178584283	chr2:179449012;179449011;179449010
Novex-1	12816	38671;38672;38673	chr2:178584285;178584284;178584283	chr2:179449012;179449011;179449010
Novex-2	12883	38872;38873;38874	chr2:178584285;178584284;178584283	chr2:179449012;179449011;179449010
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-45
• Domain position: 98
• Structural Position: 132
• Q(SASA): 0.8586
• 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
M/I	None	None	0.006	N	0.275	0.042	0.383760037723	gnomAD-4.0.0	7.13598E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.23825E-07	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
M/A	0.3293	likely_benign	0.2171	benign	-0.552	Destabilizing	None	N	0.085	neutral	None	None	None	None	N
M/C	0.7595	likely_pathogenic	0.6387	pathogenic	-0.434	Destabilizing	0.204	N	0.271	neutral	None	None	None	None	N
M/D	0.7073	likely_pathogenic	0.5432	ambiguous	0.088	Stabilizing	0.035	N	0.363	neutral	None	None	None	None	N
M/E	0.523	ambiguous	0.3817	ambiguous	0.034	Stabilizing	0.015	N	0.163	neutral	None	None	None	None	N
M/F	0.4813	ambiguous	0.3525	ambiguous	-0.203	Destabilizing	0.068	N	0.259	neutral	None	None	None	None	N
M/G	0.6258	likely_pathogenic	0.4566	ambiguous	-0.722	Destabilizing	0.007	N	0.227	neutral	None	None	None	None	N
M/H	0.5902	likely_pathogenic	0.4279	ambiguous	0.105	Stabilizing	0.439	N	0.287	neutral	None	None	None	None	N
M/I	0.454	ambiguous	0.3198	benign	-0.192	Destabilizing	0.006	N	0.275	neutral	N	0.443874761	None	None	N
M/K	0.4615	ambiguous	0.2814	benign	0.234	Stabilizing	0.011	N	0.24	neutral	N	0.409164754	None	None	N
M/L	0.163	likely_benign	0.1204	benign	-0.192	Destabilizing	0.001	N	0.127	neutral	N	0.398947761	None	None	N
M/N	0.3287	likely_benign	0.2301	benign	0.402	Stabilizing	0.035	N	0.314	neutral	None	None	None	None	N
M/P	0.6047	likely_pathogenic	0.4098	ambiguous	-0.284	Destabilizing	0.068	N	0.395	neutral	None	None	None	None	N
M/Q	0.3151	likely_benign	0.2227	benign	0.222	Stabilizing	0.068	N	0.265	neutral	None	None	None	None	N
M/R	0.5122	ambiguous	0.3121	benign	0.776	Stabilizing	0.026	N	0.388	neutral	N	0.410031546	None	None	N
M/S	0.2729	likely_benign	0.19	benign	-0.027	Destabilizing	0.001	N	0.077	neutral	None	None	None	None	N
M/T	0.1907	likely_benign	0.1372	benign	0.016	Stabilizing	None	N	0.079	neutral	N	0.346441427	None	None	N
M/V	0.1544	likely_benign	0.1159	benign	-0.284	Destabilizing	0.002	N	0.121	neutral	N	0.404449581	None	None	N
M/W	0.8	likely_pathogenic	0.6608	pathogenic	-0.174	Destabilizing	0.747	D	0.293	neutral	None	None	None	None	N
M/Y	0.6092	likely_pathogenic	0.4643	ambiguous	-0.048	Destabilizing	0.204	N	0.364	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.